2024-03-28T21:20:56Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/85452019-08-30T11:24:30Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Holtel, A
author
Goldenberg, D
author
Giladi, H
author
Oppenheim, A B
author
Timmis, K N
2007-02-19T11:33:28Z
1995-06
Journal of Bacteriology 1995 177(11):3312-3315
0021-9193
7768832
http://hdl.handle.net/10033/8545
177025
en_US
Involvement of IHF protein in expression of the Ps promoter of the Pseudomonas putida TOL plasmid.
URL
https://hzi.openrepository.com/bitstream/10033/8545/1/holtel%20et%20al_final.pdf
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MD5
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holtel et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8545/7/holtel%20et%20al_final.pdf.txt
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MD5
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holtel et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/85922019-08-30T11:37:44Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Karlson, U
author
Dwyer, D F
author
Hooper, S W
author
Moore, E R
author
Timmis, K N
author
Eltis, L D
2007-02-20T12:44:13Z
1993-03
Journal of Bacteriology 1993 175(5):1467-1474
0021-9193
8444808
http://hdl.handle.net/10033/8592
193234
Images
en_US
Two independently regulated cytochromes P-450 in a Rhodococcus rhodochrous strain that degrades 2-ethoxyphenol and 4-methoxybenzoate.
URL
https://hzi.openrepository.com/bitstream/10033/8592/1/karlson%20et%20al_final.pdf
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MD5
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1807039
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karlson et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8592/7/karlson%20et%20al_final.pdf.txt
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MD5
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karlson et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86332019-08-30T11:26:13Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Horn, Joanne M.
author
Brunke, Maren
author
Deckwer, W.-D.
author
Timmis, Kenneth N.
2007-02-20T13:30:12Z
1994-01
Applied and Environmental Microbiology 1994 60(1):357-362
0099-2240
http://hdl.handle.net/10033/8633
201314
Images
en_US
Copyright © 1994, American Society for Microbiology
Pseudomonas putida Strains Which Constitutively Overexpress Mercury Resistance for Biodetoxification of Organomercurial Pollutants
URL
https://hzi.openrepository.com/bitstream/10033/8633/1/Horn%20et%20al_final.pdf
File
MD5
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1254019
application/pdf
Horn et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8633/7/Horn%20et%20al_final.pdf.txt
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MD5
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31257
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Horn et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86342019-08-30T11:25:43Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Holtel, A
author
Marqués, S
author
Möhler, I
author
Jakubzik, U
author
Timmis, K N
2007-02-20T13:30:56Z
1994-03
Journal of Bacteriology 1994 176(6):1773-1776
0021-9193
8132475
http://hdl.handle.net/10033/8634
205268
Images
en_US
Carbon source-dependent inhibition of xyl operon expression of the Pseudomonas putida TOL plasmid.
URL
https://hzi.openrepository.com/bitstream/10033/8634/1/holtel-marques%20et%20al_final.pdf
File
MD5
b6b67fc15dbbf6a78dec6dac0c3842e7
882089
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holtel-marques et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8634/7/holtel-marques%20et%20al_final.pdf.txt
File
MD5
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21117
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holtel-marques et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86362019-08-30T11:32:36Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Kessler, B
author
Herrero, M
author
Timmis, K N
author
de Lorenzo, V
2007-02-20T13:32:28Z
1994-06
Journal of Bacteriology 1994 176(11):3171-3176
0021-9193
8195070
http://hdl.handle.net/10033/8636
205485
en_US
Genetic evidence that the XylS regulator of the Pseudomonas TOL meta operon controls the Pm promoter through weak DNA-protein interactions.
URL
https://hzi.openrepository.com/bitstream/10033/8636/1/kessler-herrero%20et%20al_final.pdf
File
MD5
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1259525
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kessler-herrero et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8636/7/kessler-herrero%20et%20al_final.pdf.txt
File
MD5
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kessler-herrero et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86402019-08-30T11:26:13Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Happe, B
author
Eltis, L D
author
Poth, H
author
Hedderich, R
author
Timmis, K N
2007-02-20T13:35:00Z
1993-11
Journal of Bacteriology 1993 175(22):7313-7320
0021-9193
8226678
http://hdl.handle.net/10033/8640
206875
Images
en_US
Characterization of 2,2',3-trihydroxybiphenyl dioxygenase, an extradiol dioxygenase from the dibenzofuran- and dibenzo-p-dioxin-degrading bacterium Sphingomonas sp. strain RW1.
URL
https://hzi.openrepository.com/bitstream/10033/8640/1/happe%20et%20al_final.pdf
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MD5
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happe et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8640/7/happe%20et%20al_final.pdf.txt
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MD5
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41007
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happe et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86492019-08-30T11:25:43Zcom_10033_6855com_10033_6839col_10033_6856
Helmholtz Zentrum für Infektionsforschung Repository
author
Struck, F
author
Collins, J
2007-02-20T13:39:43Z
1994-05-25
Nucleic Acids Research 1994 22(10):1923-1924
0305-1048
7516066
http://hdl.handle.net/10033/8649
308097
Images
en_US
Simple and rapid 5' and 3' extension techniques in RT-PCR.
URL
https://hzi.openrepository.com/bitstream/10033/8649/1/Struck%20and%20Collins_final.pdf
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MD5
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Struck and Collins_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8649/7/Struck%20and%20Collins_final.pdf.txt
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MD5
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292
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Struck and Collins_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86522019-08-30T11:25:39Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Schmeisser, C.
author
Stöckigt, C.
author
Raasch, C.
author
Wingender, J.
author
Timmis, K. N.
author
Wenderoth, D. F.
author
Flemming, H.-C.
author
Liesegang, H.
author
Schmitz, R. A.
author
Jaeger, K.-E.
author
Streit, W. R.
2007-02-20T13:41:30Z
2003-12
Applied and Environmental Microbiology 2003 69(12):7298-7309
0099-2240
14660379
10.1128/AEM.69.12.7298-7309.2003
http://hdl.handle.net/10033/8652
309957
en_US
Copyright © 2003, American Society for Microbiology
Metagenome Survey of Biofilms in Drinking-Water Networks
URL
https://hzi.openrepository.com/bitstream/10033/8652/1/schmeisser%20et%20al_final.pdf
File
MD5
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schmeisser et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8652/7/schmeisser%20et%20al_final.pdf.txt
File
MD5
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schmeisser et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86712019-08-30T11:24:26Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Ferrer, Manuel
author
Chernikova, Tatyana N.
author
Timmis, Kenneth N.
author
Golyshin, Peter N.
2007-02-20T14:41:33Z
2004-08
Applied and Environmental Microbiology 2004 70(8):4499-4504
0099-2240
15294778
10.1128/AEM.70.8.4499-4504.2004
http://hdl.handle.net/10033/8671
492381
en_US
Copyright © 2004, American Society for Microbiology
Expression of a Temperature-Sensitive Esterase in a Novel Chaperone-Based Escherichia coli Strain
URL
https://hzi.openrepository.com/bitstream/10033/8671/1/Ferrer%20et%20al_final.pdf
File
MD5
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263044
application/pdf
Ferrer et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8671/7/Ferrer%20et%20al_final.pdf.txt
File
MD5
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41528
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Ferrer et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/86942019-08-30T11:26:13Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
de Lorenzo, V
author
Herrero, M
author
Metzke, M
author
Timmis, K N
2007-02-21T08:32:46Z
1991-05
The EMBO Journal 1991 10(5):1159-1167
0261-4189
2022186
http://hdl.handle.net/10033/8694
452769
Images
en_US
An upstream XylR- and IHF-induced nucleoprotein complex regulates the sigma 54-dependent Pu promoter of TOL plasmid.
URL
https://hzi.openrepository.com/bitstream/10033/8694/1/de%20Lorenzo%20et%20al_final.pdf
File
MD5
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2322332
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de Lorenzo et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8694/7/de%20Lorenzo%20et%20al_final.pdf.txt
File
MD5
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de Lorenzo et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/87792019-08-30T11:30:30Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sabirova, Julia S
author
Ferrer, Manuel
author
Regenhardt, Daniela
author
Timmis, Kenneth N.
author
Golyshin, Peter N.
2007-02-22T15:58:58Z
2006-06
Journal of Bacteriology 2006 188(11):3763-3773
0021-9193
16707669
10.1128/JB.00072-06
http://hdl.handle.net/10033/8779
1482905
en_US
Copyright © 2006, American Society for Microbiology
Proteomic Insights into Metabolic Adaptations in Alcanivorax borkumensis Induced by Alkane Utilization
URL
https://hzi.openrepository.com/bitstream/10033/8779/1/Sabirova_fin.pdf
File
MD5
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995501
application/pdf
Sabirova_fin.pdf
URL
https://hzi.openrepository.com/bitstream/10033/8779/4/Sabirova_fin.pdf.txt
File
MD5
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64898
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Sabirova_fin.pdf.txt
oai:repository.helmholtz-hzi.de:10033/123572019-08-30T11:37:23Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Nalca, Yusuf
author
Jänsch, Lothar
author
Bredenbruch, Florian
author
Geffers, Robert
author
Buer, Jan
author
Häussler, Susanne
2007-06-20T12:08:58Z
2006-05-01
Antimicrob. Agents Chemother. 2006, 50(5):1680-8
0066-4804
16641435
10.1128/AAC.50.5.1680-1688.2006
http://hdl.handle.net/10033/12357
The administration of macrolides such as azithromycin for chronic pulmonary infection of cystic fibrosis patients has been reported to be of benefit. Although the mechanisms of action remain obscure, anti-inflammatory effects as well as interference of the macrolide with Pseudomonas aeruginosa virulence factor production have been suggested to contribute to an improved clinical outcome. In this study we used a systematic approach and analyzed the impact of azithromycin on the global transcriptional pattern and the protein expression profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The most remarkable result of this study is the finding that azithromycin exhibited extensive quorum-sensing antagonistic activities. In accordance with the inhibition of the quorum-sensing systems, virulence factor production was diminished and the oxidative stress response was impaired, whereas the type III secretion system was strongly induced. Moreover, P. aeruginosa motility was reduced, which probably accounts for the previously observed impaired biofilm formation capabilities of azithromycin-treated cultures. The interference of azithromycin with quorum-sensing-dependent virulence factor production, biofilm formation, and oxidative stress resistance in P. aeruginosa holds great promise for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist macrolides should be paid more attention in the management of chronic P. aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain vital importance for more general application against chronic infections.
en
Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach.
Article
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URL
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Häußler_AAC.pdf
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oai:repository.helmholtz-hzi.de:10033/145492019-08-30T11:37:24Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Bredenbruch, Florian
author
Geffers, Robert
author
Nimtz, Manfred
author
Buer, Jan
author
Häussler, Susanne
2007-11-13T12:28:37Z
2006-08-01
Environ. Microbiol. 2006, 8(8):1318-29
1462-2912
16872396
10.1111/j.1462-2920.2006.01025.x
http://hdl.handle.net/10033/14549
Virulence factor production and the development of biofilms in Pseudomonas aeruginosa have been shown to be regulated by two hierarchically organized quorum-sensing systems activated by two types of small acyl-homoserine lactone signal molecules. Recently, a third type of bacterial signal molecule, the Pseudomonas quinolone signal (PQS), has been identified, which positively regulates a subset of genes dependent on the quorum-sensing systems. However, the molecular mechanism underlying PQS signalling has remained poorly understood. In this study the global transcriptional profile of P. aeruginosa in response to PQS revealed a marked upregulation of genes belonging to the tightly interdependent functional groups of the iron acquisition and the oxidative stress response. Remarkably, most of the differentially regulated genes, as well as the induction of rhlR, could be traced back to an iron-chelating effect of PQS. Our results amount to the elucidation of how PQS affects P. aeruginosa and have important implications for the understanding of the complex regulatory circuits involved in P. aeruginosa gene regulation.
en
The Pseudomonas aeruginosa quinolone signal (PQS) has an iron-chelating activity.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/14549/1/Bredenbruch%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/145542019-08-30T11:37:24Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Vonberg, Ralf-Peter
author
Häussler, Susanne
author
Vandamme, Peter
author
Steinmetz, Ivo
2007-11-13T14:09:50Z
2006-06-01
J. Med. Microbiol. 2006, 55(Pt 6):721-7
0022-2615
16687590
10.1099/jmm.0.46457-0
http://hdl.handle.net/10033/14554
Members of the Burkholderia cepacia complex are important bacterial pathogens in cystic fibrosis (CF) patients. The B. cepacia complex currently consists of nine genetic subgroups (genomovars) of different epidemiological relevance and possibly of different pathogenic potential in humans. In this study, a new approach was developed for the rapid identification of B. cepacia genomovar I, Burkholderia multivorans (genomovar II), Burkholderia cenocepacia (lineage III-A and III-B), Burkholderia stabilis (genomovar IV) and Burkholderia vietnamiensis (genomovar V), which cause the large majority of infections in CF patients. The method was based on the detection of differences in the recA gene sequence by using rapid-cycle PCR and genomovar-specific fluorescence resonance energy transfer (FRET) probes. The genomovar status of all 39 B. cepacia complex strains tested (genomovars I-V) was identified by melting-curve analysis. Each FRET probe produced a specific fluorescence signal only with the respective genomovar, and not with other B. cepacia complex strains and Burkholderia spp. The identification system was easy to handle and revealed B. cepacia complex genomovar I-V status from culture isolates within about 1 h.
en
Identification of Burkholderia cepacia complex pathogens by rapid-cycle PCR with fluorescent hybridization probes.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/14554/1/Vonberg_fin.pdf
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oai:repository.helmholtz-hzi.de:10033/151122019-08-30T11:35:39Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sabirova, Julia S
author
Ferrer, Manuel
author
Lünsdorf, Heinrich
author
Wray, Victor
author
Kalscheuer, Rainer
author
Steinbüchel, Alexander
author
Timmis, Kenneth N
author
Golyshin, Peter N
department
Department of Environmental Microbiology, HZI-Helmholtz Center fro Infection Research, Braunschweig, Germany. jsa05@helmholtz-hzi.de
2007-12-11T09:08:51Z
2006-12
Mutation in a "tesB-like" hydroxyacyl-coenzyme A-specific thioesterase gene causes hyperproduction of extracellular polyhydroxyalkanoates by Alcanivorax borkumensis SK2. 2006, 188 (24):8452-9 J. Bacteriol.
0021-9193
16997960
10.1128/JB.01321-06
http://hdl.handle.net/10033/15112
Journal of bacteriology
A novel mutant of the marine oil-degrading bacterium Alcanivorax borkumensis SK2, containing a mini-Tn5 transposon disrupting a "tesB-like" acyl-coenzyme A (CoA) thioesterase gene, was found to hyperproduce polyhydroxyalkanoates (PHA), resulting in the extracellular deposition of this biotechnologically important polymer when grown on alkanes. The tesB-like gene encodes a distinct novel enzyme activity, which acts exclusively on hydroxylated acyl-CoAs and thus represents a hydroxyacyl-CoA-specific thioesterase. Inactivation of this enzyme results in the rechanneling of CoA-activated hydroxylated fatty acids, the cellular intermediates of alkane degradation, towards PHA production. These findings may open up new avenues for the development of simplified biotechnological processes for the production of PHA as a raw material for the production of bioplastics.
en
Mutation in a "tesB-like" hydroxyacyl-coenzyme A-specific thioesterase gene causes hyperproduction of extracellular polyhydroxyalkanoates by Alcanivorax borkumensis SK2.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/15112/1/Sabirova2_final.pdf
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oai:repository.helmholtz-hzi.de:10033/172532019-08-30T11:30:31Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Balke, B
author
Schmoldt, S
author
Häuβler, S
author
Suerbaum, S
author
Heesemann, J
author
Hogardt, M
department
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
2008-01-31T14:50:48Z
2008-01
A German external quality survey of diagnostic microbiology of respiratory tract infections in patients with cystic fibrosis. 2008, 7 (1):7-14notJ Cyst Fibros
1569-1993
17658302
10.1016/j.jcf.2007.02.007
http://hdl.handle.net/10033/17253
BACKGROUND: The goal of this pilot study was to design an external quality assessment (EQA) scheme for German cystic fibrosis (CF) clinical microbiology laboratories. Therefore, a multicentre study of 18 German CF laboratories was performed to evaluate their proficiency in analyzing CF respiratory secretions. METHODS: Simulated clinical specimens containing a set of four frequent CF pathogens, namely two Pseudomonas aeruginosa strains differing in morphotype (mucoid versus non-mucoid) and resistotype, one Staphylococcus aureus strain and one Burkholderia multivorans strain, were distributed to each laboratory. Isolation, identification and antimicrobial susceptibility testing (AST) of any bacterial pathogen present and completion of a questionnaire about applied microbiological protocols were requested. RESULTS: Three of four strains were isolated and identified correctly by almost all laboratories. B. multivorans was once misidentified as Burkholderia cenocepacia. Fourteen laboratories failed to detect the second multidrug resistant P. aeruginosa isolate. AST errors occurred most often for P. aeruginosa 2 followed by B. multivorans, P. aeruginosa 1 and S. aureus. Evaluation of the questionnaires revealed major differences in cultivation and identification techniques applied by the participating laboratories. CONCLUSIONS: A periodical EQA programme for German CF laboratories and standardized microbiological procedures seem to be necessary to advance diagnostic microbiology employed on CF respiratory tract specimens and may help to improve anti-infective treatment and infection control practices for CF patients.
A German external quality survey of diagnostic microbiology of respiratory tract infections in patients with cystic fibrosis.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/17253/1/Balke%20et%20al_dfinal.pdf
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oai:repository.helmholtz-hzi.de:10033/187322019-08-30T11:36:33Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Kotsyurbenko, O R
author
Friedrich, M W
author
Simankova, M V
author
Nozhevnikova, A N
author
Golyshin, P N
author
Timmis, K N
author
Conrad, R
department
Institut für Mikrobiologie, Carolo-Wilhelmina Technische Universität zu Braunschweig, Biozentrum, Braunschweig, Germany. olk@helmholtz-hzi.de
2008-02-20T13:41:42Z
2007-04
shift from acetoclastic to H2-dependent methanogenesis in a west Siberian peat bog at low pH values and isolation of an acidophilic Methanobacterium strain. 2007, 73 (7):2344-8 Appl. Environ. Microbiol.
0099-2240
17277200
10.1128/AEM.02413-06
http://hdl.handle.net/10033/18732
Applied and environmental microbiology
Methane production and archaeal community composition were studied in samples from an acidic peat bog incubated at different temperatures and pH values. H(2)-dependent methanogenesis increased strongly at the lowest pH, 3.8, and Methanobacteriaceae became important except for Methanomicrobiaceae and Methanosarcinaceae. An acidophilic and psychrotolerant Methanobacterium sp. was isolated using H(2)-plus-CO(2)-supplemented medium at pH 4.5.
en
shift from acetoclastic to H2-dependent methanogenesis in a west Siberian peat bog at low pH values and isolation of an acidophilic Methanobacterium strain.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/18732/1/Kotsyurbenko%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/195922019-08-30T11:37:23Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Kalscheuer, Rainer
author
Stöveken, Tim
author
Malkus, Ursula
author
Reichelt, Rudolf
author
Golyshin, Peter N
author
Sabirova, Julia S
author
Ferrer, Manuel
author
Timmis, Kenneth N
author
Steinbüchel, Alexander
department
Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität, Corrensstrasse 3, D-48149 Münster, Germany.
2008-03-04T08:37:04Z
2007-02
Analysis of storage lipid accumulation in Alcanivorax borkumensis: Evidence for alternative triacylglycerol biosynthesis routes in bacteria. 2007, 189 (3):918-28 J. Bacteriol.
0021-9193
17122340
10.1128/JB.01292-06
http://hdl.handle.net/10033/19592
Journal of bacteriology
Marine hydrocarbonoclastic bacteria, like Alcanivorax borkumensis, play a globally important role in bioremediation of petroleum oil contamination in marine ecosystems. Accumulation of storage lipids, serving as endogenous carbon and energy sources during starvation periods, might be a potential adaptation mechanism for coping with nutrient limitation, which is a frequent stress factor challenging those bacteria in their natural marine habitats. Here we report on the analysis of storage lipid biosynthesis in A. borkumensis strain SK2. Triacylglycerols (TAGs) and wax esters (WEs), but not poly(hydroxyalkanoic acids), are the principal storage lipids present in this and other hydrocarbonoclastic bacterial species. Although so far assumed to be a characteristic restricted to gram-positive actinomycetes, substantial accumulation of TAGs corresponding to a fatty acid content of more than 23% of the cellular dry weight is the first characteristic of large-scale de novo TAG biosynthesis in a gram-negative bacterium. The acyltransferase AtfA1 (ABO_2742) exhibiting wax ester synthase/acyl-coenzyme A:diacylglycerol acyltransferase (WS/DGAT) activity plays a key role in both TAG and WE biosynthesis, whereas AtfA2 (ABO_1804) was dispensable for storage lipid formation. However, reduced but still substantial residual TAG levels in atfA1 and atfA2 knockout mutants compellingly indicate the existence of a yet unknown WS/DGAT-independent alternative TAG biosynthesis route. Storage lipids of A. borkumensis were enriched in saturated fatty acids and accumulated as insoluble intracytoplasmic inclusions exhibiting great structural variety. Storage lipid accumulation provided only a slight growth advantage during short-term starvation periods but was not required for maintaining viability and long-term persistence during extended starvation phases.
en
Analysis of storage lipid accumulation in Alcanivorax borkumensis: Evidence for alternative triacylglycerol biosynthesis routes in bacteria.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/19592/1/Kalscheuer%20et%20al_final.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/196932019-08-30T11:37:24Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Kim, Hyun-Soo
author
Golyshin, Peter N
author
Timmis, Kenneth N
department
Department of Environmental Microbiology, The Helmholtz Center for Infection Research, Braunschweig, Germany. hyun1006@korea.ac.kr
2008-03-04T15:10:31Z
2007-11
Characterization and role of a metalloprotease induced by chitin in Serratia sp. KCK. 2007, 34 (11):715-21 J. Ind. Microbiol. Biotechnol.
1367-5435
17668255
10.1007/s10295-007-0245-1
http://hdl.handle.net/10033/19693
Journal of industrial microbiology & biotechnology
A metalloprotease induced by chitin in a new chitinolytic bacterium Serratia sp. Strain KCK was purified and characterized. Compared with other Serratia enzymes, it exhibited a rather broad pH activity range (pH 5.0-8.0), and thermostability. The cognate ORF, mpr, was cloned and expressed. Its deduced amino acid sequence showed high similarity to those of bacterial zinc-binding metalloproteases and a well-conserved serralysin family motif. Pretreatment of chitin with the Mpr protein promoted chitin degradation by chitinase A, which suggests that Mpr participates in, and facilitates, chitin degradation by this microorganism.
en
Characterization and role of a metalloprotease induced by chitin in Serratia sp. KCK.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/19693/1/Kim%20et%20al_final.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/197782019-08-30T11:37:23Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Khachane, Amit N
author
Timmis, Kenneth N
author
Martins dos Santos, Vítor A P
department
Department of Environmental Microbiology, Helmholtz Center for Infection Research, Braunschweig, Germany.
2008-03-05T13:40:54Z
2007-02
Dynamics of reductive genome evolution in mitochondria and obligate intracellular microbes. 2007, 24 (2):449-56 Mol. Biol. Evol.
0737-4038
17108184
10.1093/molbev/msl174
http://hdl.handle.net/10033/19778
Molecular biology and evolution
Reductive evolution in mitochondria and obligate intracellular microbes has led to a significant reduction in their genome size and guanine plus cytosine content (GC). We show that genome shrinkage during reductive evolution in prokaryotes follows an exponential decay pattern and provide a method to predict the extent of this decay on an evolutionary timescale. We validated predictions by comparison with estimated extents of genome reduction known to have occurred in mitochondria and Buchnera aphidicola, through comparative genomics and by drawing on available fossil evidences. The model shows how the mitochondrial ancestor would have quickly shed most of its genome, shortly after its incorporation into the protoeukaryotic cell and prior to codivergence subsequent to the split of eukaryotic lineages. It also predicts that the primary rickettsial parasitic event would have occurred between 180 and 425 million years ago (MYA), an event of relatively recent evolutionary origin considering the fact that Rickettsia and mitochondria evolved from a common alphaproteobacterial ancestor. This suggests that the symbiotic events of Rickettsia and mitochondria originated at different time points. Moreover, our model results predict that the ancestor of Wigglesworthia glossinidia brevipalpis, dated around the time of origin of its symbiotic association with the tsetse fly (50-100 MYA), was likely to have been an endosymbiont itself, thus supporting an earlier proposition that Wigglesworthia, which is currently a maternally inherited primary endosymbiont, evolved from a secondary endosymbiont.
en
Dynamics of reductive genome evolution in mitochondria and obligate intracellular microbes.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/19778/1/Khachane%20et%20al_final.pdf
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Khachane et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/19778/8/Khachane%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/197932019-08-30T11:30:32Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Yakimov, Michail M
author
Timmis, Kenneth N
author
Golyshin, Peter N
department
Istituto per l'Ambiente Marino Costiero, CNR, Messina 98122, Italy.
2008-03-05T11:39:38Z
2007-06
Obligate oil-degrading marine bacteria. 2007, 18 (3):257-66 Curr. Opin. Biotechnol.
0958-1669
17493798
10.1016/j.copbio.2007.04.006
http://hdl.handle.net/10033/19793
Current opinion in biotechnology
Over the past few years, a new and ecophysiologically unusual group of marine hydrocarbon-degrading bacteria - the obligate hydrocarbonoclastic bacteria (OHCB) - has been recognized and shown to play a significant role in the biological removal of petroleum hydrocarbons from polluted marine waters. The introduction of oil or oil constituents into seawater leads to successive blooms of a relatively limited number of indigenous marine bacterial genera--Alcanivorax, Marinobacter, Thallassolituus, Cycloclasticus, Oleispira and a few others (the OHCB)--which are present at low or undetectable levels before the polluting event. The types of OHCB that bloom depend on the latitude/temperature, salinity, redox and other prevailing physical-chemical factors. These blooms result in the rapid degradation of many oil constituents, a process that can be accelerated further by supplementation with limiting nutrients. Genome sequencing and functional genomic analysis of Alcanivorax borkumensis, the paradigm of OHCB, has provided significant insights into the genomic basis of the efficiency and versatility of its hydrocarbon utilization, the metabolic routes underlying its special hydrocarbon diet, and its ecological success. These and other studies have revealed the potential of OHCB for multiple biotechnological applications that include not only oil pollution mitigation, but also biopolymer production and biocatalysis.
en
Obligate oil-degrading marine bacteria.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/19793/1/Yakimov%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/198322019-08-30T11:37:23Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Khomiakov, N V
author
Kharin, S A
author
Nechitaĭlo, T Iu
author
Golyshin, P N
author
Kurakov, A V
author
Byzov, B A
author
Zviagintsev, D G
department
Helmholtz Centre for Infection Research (formerly GBF)
2008-03-05T13:32:08Z
2008-03-05T13:32:08Z
[Reaction of microorganisms to the digestive fluid of the earthworms], 76 (1):55-65 Mikrobiologiia
0026-3656
17410875
http://hdl.handle.net/10033/19832
Mikrobiologiia
The reaction of soil bacteria and fungi to the digestive fluid of the earthworm Aporrectodea caliginosa was studied. The fluid was obtained by centrifugation of the native enzymes of the digestive tract. The inhibition of growth of certain bacteria, spores, and fungal hyphae under the effect of extracts from the anterior and middle sections of the digestive tract of A. caliginosa was discovered for the first time. In bacteria, microcolony formation was inhibited as early as 20-30 s after the application of the gut extracts, which may indicate the nonenzymatic nature of the effect. The digestive fluid exhibited the same microbicidal activity whether the earthworms were feeding on soil or sterile sand. This indicates that the microbicidal agents are formed within the earthworm's body, rather than by soil microorganisms. The effect of the digestive fluid from the anterior and middle divisions is selective in relation to different microorganisms. Of 42 strains of soil bacteria, seven were susceptible to the microbicidal action of the fluid (Alcaligenes.faecalis 345-1, Microbacterium sp. 423-1, Arthrobacter sp. 430-1, Bacillus megaterium 401-1, B. megaterium 413-1, Kluyvera ascorbata 301-1, Pseudomonas reactans 387-2). The remaining bacteria did not die in the digestive fluid. Of 13 micromycetes, the digestive fluid inhibited spore germination in Aspergillus terreus and Paecilomyces lilacinus and the growth of hyphae in Trichoderma harzianum and Penicillium decumbens. The digestive fluid stimulated spore germination in Alternaria alternata and the growth of hyphae in Penicillium chrysogenum. The reaction of the remaining micromycetes was neutral. The gut fluid from the posterior division of the abdominal tract did not possess microbicidal activity. No relation was found between the reaction of microorganisms to the effects of the digestive fluid and the taxonomic position of the microorganisms. The effects revealed are similar to those shown earlier for millipedes and wood lice in the following parameters: quick action of the digestive fluid on microorganisms, and the selectivity of the action on microorganisms revealed at the strain level. The selective effect of the digestive gut fluid of the earthworms on soil microorganisms is important for animal feeding, maintaining the homeostasis of the gut microbial community, and the formation of microbial communities in soils.
null
[Reaction of microorganisms to the digestive fluid of the earthworms]
Article
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oai:repository.helmholtz-hzi.de:10033/199122019-08-30T11:37:44Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Gattinger, Andreas
author
Höfle, Manfred G
author
Schloter, Michael
author
Embacher, Arndt
author
Böhme, Frank
author
Munch, Jean Charles
author
Labrenz, Matthias
department
Institute of Soil Ecology, GSF-National Research Center for Environment and Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany.
2008-03-06T09:55:53Z
2007-03
Traditional cattle manure application determines abundance, diversity and activity of methanogenic Archaea in arable European soil. 2007, 9 (3):612-24 Environ. Microbiol.
1462-2912
17298362
10.1111/j.1462-2920.2006.01181.x
http://hdl.handle.net/10033/19912
Environmental microbiology
Based on lipid analyses, 16S rRNA/rRNA gene single-strand conformation polymorphism fingerprints and methane flux measurements, influences of the fertilization regime on abundance and diversity of archaeal communities were investigated in soil samples from the long-term (103 years) field trial in Bad Lauchstädt, Germany. The investigated plots followed a gradient of increasing fertilization beginning at no fertilization and ending at the 'cattle manure' itself. The archaeal phospholipid etherlipid (PLEL) concentration was used as an indicator for archaeal biomass and increased with the gradient of increasing fertilization, whereby the concentrations determined for organically fertilized soils were well above previously reported values. Methane emission, although at a low level, were occasionally only observed in organically fertilized soils, whereas the other treatments showed significant methane uptake. Euryarchaeotal organisms were abundant in all investigated samples but 16S rRNA analysis also demonstrated the presence of Crenarchaeota in fertilized soils. Lowest molecular archaeal diversity was found in highest fertilized treatments. Archaea phylogenetically most closely related to cultured methanogens were abundant in these fertilized soils, whereas Archaea with low relatedness to cultured microorganisms dominated in non-fertilized soils. Relatives of Methanoculleus spp. were found almost exclusively in organically fertilized soils or cattle manure. Methanosarcina-related microorganisms were detected in all soils as well as in the cattle manure, but soils with highest organic application rate were specifically dominated by a close phylogenetic relative of Methanosarcina thermophila. Our findings suggest that regular application of cattle manure increased archaeal biomass, but reduced archaeal diversity and selected for methanogenic Methanoculleus and Methanosarcina strains, leading to the circumstance that high organic fertilized soils did not function as a methane sink at the investigated site anymore.
en
Traditional cattle manure application determines abundance, diversity and activity of methanogenic Archaea in arable European soil.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/19912/1/Gattinger%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/244322019-08-30T11:27:16Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Böckelmann, Uta
author
Lünsdorf, Heinrich
author
Szewzyk, Ulrich
department
Department of Environmental Microbiology, Technical University Berlin, Franklin Str. 29, 10587 Berlin, Germany. uta.boeckelmann@tu-berlin.de
2008-04-29T13:38:06Z
2007-09
Ultrastructural and electron energy-loss spectroscopic analysis of an extracellular filamentous matrix of an environmental bacterial isolate. 2007, 9 (9):2137-44 Environ. Microbiol.
1462-2912
17686013
10.1111/j.1462-2920.2007.01325.x
http://hdl.handle.net/10033/24432
Environmental microbiology
Strain F8, a bacterial isolate from 'river snow', was found to produce extracellular fibres in the form of a filamentous network. These extracellular filaments, which were previously shown to be composed of DNA, have been studied for the first time by ultrastructural and electron energy-loss spectroscopy in the present work. 'Whole mount' preparations of strain F8 indicate these polymers are ultrastructurally homogeneous and form a network of elemental filaments, which have a width of 1.8-2.0 nm. When incubated at pH 3.5 with colloidal cationic ThO(2) tracers they become intensely stained (electron dense), affording direct evidence that the fibres are negatively charged and thus acidic chemically. Elemental analysis of the extracellular filaments by Energy-filtered Transmission Electron Microscopy revealed phosphorus to be the main element present and, because pretreatment of F8 cells with DNase prevented thorium labelling, the fibres must be composed of extracellular DNA (eDNA). Neither ultrathin sections nor 'whole mount negative stain' caused DNA release by general cell lysis. Additionally, cells infected with phages were never observed in ultrathin sections and phage particles were never detected in whole mount samples, which rules out the possibility of phages being directly involved in eDNA release.
en
Ultrastructural and electron energy-loss spectroscopic analysis of an extracellular filamentous matrix of an environmental bacterial isolate.
Article
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oai:repository.helmholtz-hzi.de:10033/276122019-08-30T11:37:23Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Meissner, Andree
author
Wild, Verena
author
Simm, Roger
author
Rohde, Manfred
author
Erck, Christian
author
Bredenbruch, Florian
author
Morr, Michael
author
Römling, Ute
author
Häussler, Susanne
department
Division of Cell Biology and Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
2008-05-22T12:45:59Z
2007-10
Pseudomonas aeruginosa cupA-encoded fimbriae expression is regulated by a GGDEF and EAL domain-dependent modulation of the intracellular level of cyclic diguanylate. 2007, 9 (10):2475-85 Environ. Microbiol.
1462-2912
17803773
10.1111/j.1462-2920.2007.01366.x
http://hdl.handle.net/10033/27612
Environmental microbiology
Cyclic-diguanylate (c-di-GMP) is a widespread bacterial signal molecule that plays a major role in the modulation of cellular surface components, such as exopolysaccharides and fimbriae, and in the establishment of a sessile life style. Here, we report that intracellular c-di-GMP levels influence cupA-encoded fimbriae expression in Pseudomonas aeruginosa. In an autoaggregative P. aeruginosa small colony variant (SCV) CupA fimbriae and the intracellular c-di-GMP concentration were found to be enhanced as compared with the clonal wild-type. The SCV morphology and the expression of CupA fimbriae were dependent on a functional PA1120 and morA gene both encoding a GGDEF domain. Overexpression of the GGDEF domain protein PA1120 complemented the PA1120 and the morA mutant with respect to CupA fimbriae expression. In agreement with these findings, overexpression of the EAL domain containing phenotypic variance regulator (PvrR) in the SCV resulted in a decreased intracellular level of c-di-GMP, a reduced cupA fimbriae expression and a switch to wild-type colony morphology.
en
Pseudomonas aeruginosa cupA-encoded fimbriae expression is regulated by a GGDEF and EAL domain-dependent modulation of the intracellular level of cyclic diguanylate.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/27612/1/Meissner%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/303242019-08-30T11:29:47Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Blasco, Rafael
author
Ramos, Juan-Luis
author
Wittich, Rolf-Michael
department
Departamento de Bioquímica, Biología Molecular y Genética, Facultad de Veterinaria, Universidad de Extremadura, E-10071 Cáceres, Spain.
2008-06-23T14:07:51Z
2008-06
Pseudomonas aeruginosa strain RW41 mineralizes 4-chlorobenzenesulfonate, the major polar by-product from DDT manufacturing. 2008, 10 (6):1591-600 Environ. Microbiol.
1462-2920
18331335
10.1111/j.1462-2920.2008.01575.x
http://hdl.handle.net/10033/30324
Environmental microbiology
Pseudomonas aeruginosa RW41 is the first bacterial strain, which could be isolated by virtue of its capability to mineralize 4-chlorobenzenesulfonic acid (4CBSA), the major polar by-product of the chemical synthesis of 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)ethane (DDT). This capability makes the isolate a promising candidate for the development of bioremediation technologies. The bacterial mineralization of 4CBSA proceeds under oxygenolytic desulfonation and transient accumulation of sulfite which then is oxidized to sulfate. High enzyme activities for the turnover of 4-chlorocatechol were measured. The further catabolism proceeded through 3-chloromuconate and, probably, the instable 4-chloromuconolactone, which is directly hydrolyzed to maleylacetate. Detectable levels of maleylacetate reductase were only present when cells were grown with 4CBSA. When the ordinary catechol pathway was induced during growth on benzenesulfonate, catechol was ortho-cleaved to cis,cis-muconate and a partially purified muconate cycloisomerase transformed it to muconolactone in vitro. The same enzyme transformed 3-chloro-cis,cis-muconate into cis-dienelactone (76%) and the antibiotically active protoanemonin (24%). These observations are indicative for a not yet highly evolved catabolism for halogenated substrates by bacterial isolates from environmental samples which, on the other hand, are able to productively recycle sulfur and chloride ions from synthetic haloorganosulfonates.
en
Pseudomonas aeruginosa strain RW41 mineralizes 4-chlorobenzenesulfonate, the major polar by-product from DDT manufacturing.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/30324/1/Blasko_final.pdf
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oai:repository.helmholtz-hzi.de:10033/360322019-08-30T11:32:17Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Fahy, A
author
Ball, A S
author
Lethbridge, G
author
Timmis, K N
author
McGenity, T J
department
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, UK. afahy@essex.ac.uk
2008-08-21T08:37:58Z
2008-07
Isolation of alkali-tolerant benzene-degrading bacteria from a contaminated aquifer. 2008, 47 (1):60-6 Lett. Appl. Microbiol.
1472-765X
18544140
10.1111/j.1472-765X.2008.02386.x
http://hdl.handle.net/10033/36032
Letters in applied microbiology
AIMS: To isolate benzene-degrading strains from neutral and alkaline groundwaters contaminated by benzene, toluene, ethylbenzene, xylenes (BTEX) from the SIReN aquifer, UK, and to test their effective pH range and ability to degrade TEX. METHODS AND RESULTS: The 14 isolates studied had an optimum pH for growth of 8, and could degrade benzene to below detection level (1 microg l(-1)). Five Rhodococcus erythropolis strains were able to metabolize benzene up to pH 9, two distinct R. erythropolis strains to pH 10, and one Arthrobacter strain to pH 8.5. These Actinobacteria also degraded benzene at least down to pH 5.5. Six other isolates, a Hydrogenophaga and five Pseudomonas strains, had a narrower pH tolerance for benzene degradation (pH 6 to 8.5), and could metabolize toluene; in addition, the Hydrogenophaga and two Pseudomonas strains utilized o-, m- or p-xylenes. None of these strains degraded ethylbenzene. CONCLUSIONS: Phylogenetically distinct isolates, able to degrade BTX compounds, were obtained, and some degraded benzene at high pH. SIGNIFICANCE AND IMPACT OF THE STUDY: High pH has previously been found to inhibit in situ degradation of benzene, a widespread, carcinogenic groundwater contaminant. These benzene-degrading organisms therefore have potential applications in the remediation or natural attenuation of alkaline waters.
en
Isolation of alkali-tolerant benzene-degrading bacteria from a contaminated aquifer.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/485412019-08-30T11:32:17Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sabirova, Julia S
author
Ferrer, Manuel
author
Regenhardt, Daniela
author
Timmis, Kenneth N
author
Golyshin, Peter N
department
Institute of Microbiology, Technical University of Braunschweig, Spielmannstrasse 7, D-38106 Braunschweig, Germany. jsa05@gbf.de
2009-02-05T14:47:27Z
2006-06
Proteomic insights into metabolic adaptations in Alcanivorax borkumensis induced by alkane utilization. 2006, 188 (11):3763-73 J. Bacteriol.
0021-9193
16707669
10.1128/JB.00072-06
http://hdl.handle.net/10033/48541
Journal of bacteriology
Alcanivorax borkumensis is a ubiquitous marine petroleum oil-degrading bacterium with an unusual physiology specialized for alkane metabolism. This "hydrocarbonoclastic" bacterium degrades an exceptionally broad range of alkane hydrocarbons but few other substrates. The proteomic analysis presented here reveals metabolic features of the hydrocarbonoclastic lifestyle. Specifically, hexadecane-grown and pyruvate-grown cells differed in the expression of 97 cytoplasmic and membrane-associated proteins whose genes appeared to be components of 46 putative operon structures. Membrane proteins up-regulated in alkane-grown cells included three enzyme systems able to convert alkanes via terminal oxidation to fatty acids, namely, enzymes encoded by the well-known alkB1 gene cluster and two new alkane hydroxylating systems, a P450 cytochrome monooxygenase and a putative flavin-binding monooxygenase, and enzymes mediating beta-oxidation of fatty acids. Cytoplasmic proteins up-regulated in hexadecane-grown cells reflect a central metabolism based on a fatty acid diet, namely, enzymes of the glyoxylate bypass and of the gluconeogenesis pathway, able to provide key metabolic intermediates, like phosphoenolpyruvate, from fatty acids. They also include enzymes for synthesis of riboflavin and of unsaturated fatty acids and cardiolipin, which presumably reflect membrane restructuring required for membranes to adapt to perturbations induced by the massive influx of alkane oxidation enzymes. Ancillary functions up-regulated included the lipoprotein releasing system (Lol), presumably associated with biosurfactant release, and polyhydroxyalkanoate synthesis enzymes associated with carbon storage under conditions of carbon surfeit. The existence of three different alkane-oxidizing systems is consistent with the broad range of oil hydrocarbons degraded by A. borkumensis and its ecological success in oil-contaminated marine habitats.
en
Proteomic insights into metabolic adaptations in Alcanivorax borkumensis induced by alkane utilization.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/48541/1/Sabirova%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/500532019-08-30T11:25:43Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Golyshina, Olga V
author
Golyshin, Peter N
author
Timmis, Kenneth N
author
Ferrer, Manuel
department
Division of Microbiology, GBF--German Research Centre for Biotechnology, Braunschweig, Germany.
2009-02-23T14:17:40Z
2006-03
The 'pH optimum anomaly' of intracellular enzymes of Ferroplasma acidiphilum. 2006, 8 (3):416-25 Environ. Microbiol.
1462-2912
16478448
10.1111/j.1462-2920.2005.00907.x
http://hdl.handle.net/10033/50053
Environmental microbiology
A wide range of microorganisms, the so-called acidophiles, inhabit acidic environments and grow optimally at pH values between 0 and 3. The intracellular pH of these organisms is, however, close to neutrality or slightly acidic. It is to be expected that enzymatic activities dedicated to extracellular functions would be adapted to the prevailing low pH of the environment (0-3), whereas intracellular enzymes would be optimally active at the near-neutral pH of the cytoplasm (4.6-7.0). The genes of several intracellular or cell-bound enzymes, a carboxylesterase and three alpha-glucosidases, from Ferroplasma acidiphilum, a cell wall-lacking acidophilic archaeon with a growth optimum at pH 1.7, were cloned and expressed in Escherichia coli, and their products purified and characterized. The Ferroplasmaalpha-glucosidases exhibited no sequence similarity to known glycosyl hydrolases. All enzymes functioned and were stable in vitro in the pH range 1.7-4.0, and had pH optima much lower than the mean intracellular pH of 5.6. This 'pH optimum anomaly' suggests the existence of yet-undetected cellular compartmentalization providing cytoplasmic pH patchiness and low pH environments for the enzymes we have analysed.
en
The 'pH optimum anomaly' of intracellular enzymes of Ferroplasma acidiphilum.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/50053/1/Golyshina%20et%20al_final.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/705962019-08-30T11:37:23Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Dötsch, Andreas
author
Pommerenke, Claudia
author
Bredenbruch, Florian
author
Geffers, Robert
author
Häussler, Susanne
department
Helmholtz Centre for Infection Research, Braunschweig, Germany. andreas.doetsch@helmholtz-hzi.de
2009-06-16T13:09:44Z
2009
Evaluation of a microarray-hybridization based method applicable for discovery of single nucleotide polymorphisms (SNPs) in the Pseudomonas aeruginosa genome. 2009, 10:29 BMC Genomics
1471-2164
19152677
10.1186/1471-2164-10-29
http://hdl.handle.net/10033/70596
BMC genomics
BACKGROUND: Whole genome sequencing techniques have added a new dimension to studies on bacterial adaptation, evolution and diversity in chronic infections. By using this powerful approach it was demonstrated that Pseudomonas aeruginosa undergoes intense genetic adaptation processes, crucial in the development of persistent disease. The challenge ahead is to identify universal infection relevant adaptive bacterial traits as potential targets for the development of alternative treatment strategies. RESULTS: We developed a microarray-based method applicable for discovery of single nucleotide polymorphisms (SNPs) in P. aeruginosa as an easy and economical alternative to whole genome sequencing. About 50% of all SNPs theoretically covered by the array could be detected in a comparative hybridization of PAO1 and PA14 genomes at high specificity (> 0.996). Variations larger than SNPs were detected at much higher sensitivities, reaching nearly 100% for genetic differences affecting multiple consecutive probe oligonucleotides. The detailed comparison of the in silico alignment with experimental hybridization data lead to the identification of various factors influencing sensitivity and specificity in SNP detection and to the identification of strain specific features such as a large deletion within the PA4684 and PA4685 genes in the Washington Genome Center PAO1. CONCLUSION: The application of the genome array as a tool to identify adaptive mutations, to depict genome organizations, and to identify global regulons by the "ChIP-on-chip" technique will expand our knowledge on P. aeruginosa adaptation, evolution and regulatory mechanisms of persistence on a global scale and thus advance the development of effective therapies to overcome persistent disease.
en
Evaluation of a microarray-hybridization based method applicable for discovery of single nucleotide polymorphisms (SNPs) in the Pseudomonas aeruginosa genome.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/70596/1/D%c3%b6tsch%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/705952019-08-30T11:37:23Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Moya, Bartolomé
author
Dötsch, Andreas
author
Juan, Carlos
author
Blázquez, Jesús
author
Zamorano, Laura
author
Haussler, Susanne
author
Oliver, Antonio
department
Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, Instituto Universitario de Investigación en Ciencias de la Salud Palma de Mallorca, Spain.
2009-06-16T13:05:46Z
2009-03
Beta-lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein. 2009, 5 (3):e1000353 PLoS Pathog.
1553-7374
19325877
10.1371/journal.ppat.1000353
http://hdl.handle.net/10033/70595
PLoS pathogens
It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for beta-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in beta-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) beta-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for beta-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex beta-lactam resistance response, triggering overproduction of the chromosomal beta-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of beta-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases.
en
Beta-lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/70595/1/Moya%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/785132019-08-30T11:37:44Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Dötsch, Andreas
author
Becker, Tanja
author
Pommerenke, Claudia
author
Magnowska, Zofia
author
Jänsch, Lothar
author
Häussler, Susanne
department
Chronic Pseudomonas Infections Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
2009-08-25T14:04:44Z
2009-06
Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa. 2009, 53 (6):2522-31 Antimicrob. Agents Chemother.
1098-6596
19332674
10.1128/AAC.00035-09
http://hdl.handle.net/10033/78513
Antimicrobial agents and chemotherapy
The emergence of antimicrobial drug resistance is of enormous public concern due to the increased risk of delayed treatment of infections, the increased length of hospital stays, the substantial increase in the cost of care, and the high risk of fatal outcomes. A prerequisite for the development of effective therapy alternatives is a detailed understanding of the diversity of bacterial mechanisms that underlie drug resistance, especially for problematic gram-negative bacteria such as Pseudomonas aeruginosa. This pathogen has impressive chromosomally encoded mechanisms of intrinsic resistance, as well as the potential to mutate, gaining resistance to current antibiotics. In this study we have screened the comprehensive nonredundant Harvard PA14 library for P. aeruginosa mutants that exhibited either increased or decreased resistance against 19 antibiotics commonly used in the clinic. This approach identified several genes whose inactivation sensitized the bacteria to a broad spectrum of different antimicrobials and uncovered novel genetic determinants of resistance to various classes of antibiotics. Knowledge of the enhancement of bacterial susceptibility to existing antibiotics and of novel resistance markers or modifiers of resistance expression may lay the foundation for effective therapy alternatives and will be the basis for the development of new strategies in the control of problematic multiresistant gram-negative bacteria.
en
Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/78513/1/D%c3%b6tsch%20et%20al_final.pdf
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https://hzi.openrepository.com/bitstream/10033/78513/7/D%c3%b6tsch%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/902582019-08-30T11:35:14Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Golyshina, Olga V
author
Yakimov, Michail M
author
Lünsdorf, Heinrich
author
Ferrer, Manuel
author
Nimtz, Manfred
author
Timmis, Kenneth N
author
Wray, Victor
author
Tindall, Brian J
author
Golyshin, Peter N
department
Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. p.golyshin@bangor.ac.uk
2010-01-21T10:17:38Z
2009-11
Acidiplasma aeolicum gen. nov., sp. nov., a euryarchaeon of the family Ferroplasmaceae isolated from a hydrothermal pool, and transfer of Ferroplasma cupricumulans to Acidiplasma cupricumulans comb. nov. 2009, 59 (Pt 11):2815-23 Int. J. Syst. Evol. Microbiol.
1466-5026
19628615
10.1099/ijs.0.009639-0
http://hdl.handle.net/10033/90258
International journal of systematic and evolutionary microbiology
A novel acidophilic, cell-wall-less archaeon, strain V(T), was isolated from a hydrothermal pool on Vulcano Island, Italy. The morphology of cells was observed to vary from pleomorphic to coccoid. The temperature range for growth of strain V(T) was 15-65 degrees C with an optimum at 45 degrees C. The pH for growth ranged from pH 0 to 4 with an optimal at pH 1.4-1.6. Strain V(T) was able to grow aerobically and anaerobically, oxidizing ferrous iron and reducing ferric iron, respectively. The isolate grew chemo-organotrophically with yeast extract and yeast extract with glucose as the sources of energy and carbon. The molar G+C content in the DNA was 36 mol%. 16S rRNA gene sequence analysis demonstrated that strain V(T) was a member of the family Ferroplasmaceae, order Thermoplasmatales, phylum Euryarchaeota, showing sequence identities of 100 % with Ferroplasma cupricumulans BH2(T), 95.4 % with Ferroplasma acidiphilum Y(T), 94 % with Picrophilus torridus DSM 9790(T) and 92 % with Picrophilus oshimae DSM 9789(T). 16S rRNA gene sequence-based phylogenetic analysis showed that strain V(T) formed a monophyletic cluster together with F. cupricumulans BH2(T) and all other thermophilic isolates with available 16S rRNA gene sequences, whereas F. acidiphilum Y(T) formed another cluster with mesophilic isolates within the family Ferroplasmaceae. DNA-DNA hybridization values between strain V(T) and F. cupricumulans BH2(T) were well below 70 %, indicating that the two strains belong to separate species. Principal membrane lipids of strain V(T) were dibiphytanyl-based tetraether lipids containing pentacyclic rings. The polar lipids were dominated by a single phosphoglycolipid derivative based on a galactosyl dibiphytanyl phosphoglycerol tetraether, together with smaller amounts of monoglycosyl and diglycosyl dibiphytanyl ether lipids and the corresponding phosphoglycerol derivatives. The major respiratory quinones present were naphthoquinone derivatives. Given the notable physiological and chemical differences as well as the distinct phylogenetic placement of the new isolate relative to the type species of the genus Ferroplasma, we propose strain V(T) as a member of a new genus and species, Acidiplasma aeolicum gen. nov., sp. nov. The type strain of Acidiplasma aeolicum is strain V(T) (=DSM 18409(T) =JCM 14615(T)). In addition, we propose to transfer Ferroplasma cupricumulans Hawkes et al. 2008 to the genus Acidiplasma as Acidiplasma cupricumulans comb. nov. (type strain BH2(T) =DSM 16551(T) =JCM 13668(T)).
en
Acidiplasma aeolicum gen. nov., sp. nov., a euryarchaeon of the family Ferroplasmaceae isolated from a hydrothermal pool, and transfer of Ferroplasma cupricumulans to Acidiplasma cupricumulans comb. nov.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/90258/1/Golyshina%20et%20al_final.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/90258/4/Golyshina%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/963152019-08-30T11:33:30Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Alvarez, Laura Acuña
author
Exton, Daniel A
author
Timmis, Kenneth N
author
Suggett, David J
author
McGenity, Terry J
department
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.
2010-04-12T14:34:29Z
2009-12
Characterization of marine isoprene-degrading communities. 2009, 11 (12):3280-91 Environ. Microbiol.
1462-2920
19807779
10.1111/j.1462-2920.2009.02069.x
http://hdl.handle.net/10033/96315
Environmental microbiology
Isoprene is a volatile and climate-altering hydrocarbon with an atmospheric concentration similar to that of methane. It is well established that marine algae produce isoprene; however, until now there was no specific information about marine isoprene sinks. Here we demonstrate isoprene consumption in samples from temperate and tropical marine and coastal environments, and furthermore show that the most rapid degradation of isoprene coincides with the highest rates of isoprene production in estuarine sediments. Isoprene-degrading enrichment cultures, analysed by denaturing gradient gel electrophoresis and 454 pyrosequencing of the 16S rRNA gene and by culturing, were generally dominated by Actinobacteria, but included other groups such as Alphaproteobacteria and Bacteroidetes, previously not known to degrade isoprene. In contrast to specialist methane-oxidizing bacteria, cultivated isoprene degraders were nutritionally versatile, and nearly all of them were able to use n-alkanes as a source of carbon and energy. We therefore tested and showed that the ubiquitous marine hydrocarbon-degrader, Alcanivorax borkumensis, could also degrade isoprene. A mixture of the isolates consumed isoprene emitted from algal cultures, confirming that isoprene can be metabolized at low, environmentally relevant concentrations, and suggesting that, in the absence of spilled petroleum hydrocarbons, algal production of isoprene could maintain viable populations of hydrocarbon-degrading microbes. This discovery of a missing marine sink for isoprene is the first step in obtaining more robust predictions of its flux, and suggests that algal-derived isoprene provides an additional source of carbon for diverse microbes in the oceans.
en
Characterization of marine isoprene-degrading communities.
Article
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oai:repository.helmholtz-hzi.de:10033/1219162019-08-30T11:31:49Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Martin-Arjol, I
author
Bassas-Galia, M
author
Bermudo, E
author
Garcia, F
author
Manresa, A
department
Laboratori de Microbiologia, Facultat de Farmàcia, Universitat de Barcelona, Joan XXIII s/n, Barcelona, Spain.
2011-02-15T10:08:09Z
2010-05
Identification of oxylipins with antifungal activity by LC-MS/MS from the supernatant of Pseudomonas 42A2. 2010, 163 (4-5):341-6 Chem. Phys. Lipids
1873-2941
20188718
10.1016/j.chemphyslip.2010.02.003
http://hdl.handle.net/10033/121916
Chemistry and physics of lipids
In microorganisms hydroxy fatty acids are produced from the biotransformation of unsaturated fatty acids. Such compounds belong to a class of oxylipins which are reported to perform a variety of biological functions such as anti-inflammatory or cytotoxic activity. These compounds have been found in rice and timothy plants after being infected by specific fungus. When grown in submerged culture with linoleic acid, Pseudomonas 42A2 accumulated in the supernatant several hydroxy fatty acids. In this work LC-MS/MS has been used to elucidate the structure of the components form the organic extract: 9-hydroxy-10,12-octadecadienoic acid; 13-hydroxy-9,11-octadecadienoic acid; 7,10-dihydroxy-8E-octadecenoic acid; 9,10,13-trihydroxy-11-octadecenoic acid and 9,12,13-trihydroxy-10-octadecenoic acid. Antimicrobial activity against several pathogenic fungal strains is presented: MIC (microg/mL) Verticillium dhaliae, 32; Macrophonia phaesolina, 32; Arthroderma uncinatum, 32; Trycophyton mentagrophytes, 64.
en
Identification of oxylipins with antifungal activity by LC-MS/MS from the supernatant of Pseudomonas 42A2.
Article
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oai:repository.helmholtz-hzi.de:10033/1220452019-08-30T11:37:23Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Pommerenke, Claudia
author
Müsken, Mathias
author
Becker, Tanja
author
Dötsch, Andreas
author
Klawonn, Frank
author
Häussler, Susanne
department
Chronic Pseudomonas Infections, Helmholtz Center for Infection Research, Braunschweig, Germany.
2011-02-16T08:50:48Z
2010
Global genotype-phenotype correlations in Pseudomonas aeruginosa. 2010, 6 (8) PLoS Pathog.
1553-7374
20865161
10.1371/journal.ppat.1001074
http://hdl.handle.net/10033/122045
PLoS pathogens
Once the genome sequence of an organism is obtained, attention turns from identifying genes to understanding their function, their organization and control of metabolic pathways and networks that determine its physiology. Recent technical advances in acquiring genome-wide data have led to substantial progress in identifying gene functions. However, we still do not know the function of a large number of genes and, even when a gene product has been assigned to a functional class, we cannot normally predict its contribution to the phenotypic behaviour of the cell or organism--the phenome. In this study, we assessed bacterial growth parameters of 4030 non-redundant PA14 transposon mutants in the pathogenic bacterium Pseudomonas aeruginosa. The genome-wide simultaneous analysis of 119 distinct growth-related phenotypes uncovered a comprehensive phenome and provided evidence that most genotypes are not phenotypically isolated but rather define specific complex phenotypic clusters of genotypes. Since phenotypic overlap was demonstrated to reflect the relatedness of genotypes on a global scale, knowledge of an organism's phenome might significantly contribute to the advancement of functional genomics.
en
Global genotype-phenotype correlations in Pseudomonas aeruginosa.
Article
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oai:repository.helmholtz-hzi.de:10033/1240272019-08-30T11:26:42Zcom_10033_311624com_10033_6839com_10033_311308col_10033_311625col_10033_620721
Helmholtz Zentrum für Infektionsforschung Repository
author
Solbak, Sara M
author
Reksten, Tove R
author
Wray, Victor
author
Bruns, Karsten
author
Horvli, Ole
author
Raae, Arnt J
author
Henklein, Petra
author
Henklein, Peter
author
Röder, Rene
author
Mitzner, David
author
Schubert, Ulrich
author
Fossen, Torgils
department
Department of Chemistry, University of Bergen, N-5007 Bergen, Norway.
2011-03-09T10:13:45Z
2010
The intriguing cyclophilin A-HIV-1 Vpr interaction: prolyl cis/trans isomerisation catalysis and specific binding. 2010, 10:31 BMC Struct. Biol.
1472-6807
20920334
10.1186/1472-6807-10-31
http://hdl.handle.net/10033/124027
BMC structural biology
Cyclophilin A (CypA) represents a potential target for antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication, although the mechanism through which CypA modulates HIV-1 infectivity still remains unclear. The interaction of HIV-1 viral protein R (Vpr) with the human peptidyl prolyl isomerase CypA is known to occur in vitro and in vivo. However, the nature of the interaction of CypA with Pro-35 of N-terminal Vpr has remained undefined.
en
The intriguing cyclophilin A-HIV-1 Vpr interaction: prolyl cis/trans isomerisation catalysis and specific binding.
Article
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oai:repository.helmholtz-hzi.de:10033/1288112019-08-30T11:37:24Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Schmidt, Juliane
author
Müsken, Mathias
author
Becker, Tanja
author
Magnowska, Zofia
author
Bertinetti, Daniela
author
Möller, Stefan
author
Zimmermann, Bastian
author
Herberg, Friedrich W
author
Jänsch, Lothar
author
Häussler, Susanne
department
Department of Cell Biology, Helmholtz Center for Infection Research, Braunschweig, Germany.
2011-04-28T08:12:05Z
2011
The Pseudomonas aeruginosa Chemotaxis Methyltransferase CheR1 Impacts on Bacterial Surface Sampling. 2011, 6 (3):e18184 PLoS ONE
1932-6203
21445368
10.1371/journal.pone.0018184
http://hdl.handle.net/10033/128811
PloS one
The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa.
en
The Pseudomonas aeruginosa Chemotaxis Methyltransferase CheR1 Impacts on Bacterial Surface Sampling.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/1456112019-08-30T11:30:32Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sabirova, Julia S
author
Becker, Anke
author
Lünsdorf, Heinrich
author
Nicaud, Jean-Marc
author
Timmis, Kenneth N
author
Golyshin, Peter N
department
Department of Bioscience and Bioengineering, Ghent University, Ghent, Belgium. julia.sabirova@ugent.be
2011-10-18T08:39:23Z
2011-06
Transcriptional profiling of the marine oil-degrading bacterium Alcanivorax borkumensis during growth on n-alkanes. 2011, 319 (2):160-8 FEMS Microbiol. Lett.
1574-6968
21470299
10.1111/j.1574-6968.2011.02279.x
http://hdl.handle.net/10033/145611
FEMS microbiology letters
The marine oil-degrading bacterium Alcanivorax borkumensis SK2 has attracted significant interest due to its hydrocarbonoclastic lifestyle, its alkane-centered metabolism, and for playing an important ecological role in cleaning up marine oil spills. In this study, we used microarray technology to characterize the transcriptional responses of A. borkumensis to n-hexadecane exposure as opposed to pyruvate, which led to the identification of a total of 220 differentially expressed genes, with 109 genes being upregulated and 111 genes being downregulated. Among the genes upregulated on alkanes are systems predicted to be involved in the terminal oxidation of alkanes, biofilm formation, signal transduction, and regulation.
en
Transcriptional profiling of the marine oil-degrading bacterium Alcanivorax borkumensis during growth on n-alkanes.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/1456892019-08-30T11:37:44Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Matz, Carsten
author
Nouri, Bianka
author
McCarter, Linda
author
Martinez-Urtaza, Jaime
department
Helmholtz Centre for Infection Research, Braunschweig, Germany.
2011-10-18T14:27:29Z
2011
Acquired type III secretion system determines environmental fitness of epidemic Vibrio parahaemolyticus in the interaction with bacterivorous protists. 2011, 6 (5):e20275 PLoS ONE
1932-6203
21629787
10.1371/journal.pone.0020275
http://hdl.handle.net/10033/145689
PloS one
Genome analyses of marine microbial communities have revealed the widespread occurrence of genomic islands (GIs), many of which encode for protein secretion machineries described in the context of bacteria-eukaryote interactions. Yet experimental support for the specific roles of such GIs in aquatic community interactions remains scarce. Here, we test for the contribution of type III secretion systems (T3SS) to the environmental fitness of epidemic Vibrio parahaemolyticus. Comparisons of V. parahaemolyticus wild types and T3SS-defective mutants demonstrate that the T3SS encoded on genome island VPaI-7 (T3SS-2) promotes survival of V. parahaemolyticus in the interaction with diverse protist taxa. Enhanced persistence was found to be due to T3SS-2 mediated cytotoxicity and facultative parasitism of V. parahaemolyticus on coexisting protists. Growth in the presence of bacterivorous protists and the T3SS-2 genotype showed a strong correlation across environmental and clinical isolates of V. parahaemolyticus. Short-term microcosm experiments provide evidence that protistan hosts facilitate the invasion of T3SS-2 positive V. parahaemolyticus into a coastal plankton community, and that water temperature and productivity further promote enhanced survival of T3SS-2 positive V. parahaemolyticus. This study is the first to describe the fitness advantage of GI-encoded functions in a microbial food web, which may provide a mechanistic explanation for the global spread and the seasonal dynamics of V. parahaemolyticus pathotypes, including the pandemic serotype cluster O3:K6, in aquatic environments.
en
Acquired type III secretion system determines environmental fitness of epidemic Vibrio parahaemolyticus in the interaction with bacterivorous protists.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/145689/1/Matz%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/2369892019-08-30T11:25:43Zcom_10033_311624com_10033_6839com_10033_620636col_10033_311625col_10033_620638
Helmholtz Zentrum für Infektionsforschung Repository
author
Göhler, Anna-Katharina
author
Kökpinar, Öznur
author
Schmidt-Heck, Wolfgang
author
Geffers, Robert
author
Guthke, Reinhard
author
Rinas, Ursula
author
Schuster, Stefan
author
Jahreis, Knut
author
Kaleta, Christoph
department
Department of Genetics, University of Osnabrück, Osnabrück, Germany.
2012-08-02T10:34:07Z
2011
More than just a metabolic regulator--elucidation and validation of new targets of PdhR in Escherichia coli. 2011, 5:197 BMC Syst Biol
1752-0509
22168595
10.1186/1752-0509-5-197
http://hdl.handle.net/10033/236989
BMC systems biology
The pyruvate dehydrogenase regulator protein (PdhR) of Escherichia coli acts as a transcriptional regulator in a pyruvate dependent manner to control central metabolic fluxes. However, the complete PdhR regulon has not yet been uncovered. To achieve an extended understanding of its gene regulatory network, we combined large-scale network inference and experimental verification of results obtained by a systems biology approach.
en
Archived with thanks to BMC systems biology
More than just a metabolic regulator--elucidation and validation of new targets of PdhR in Escherichia coli.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/236989/1/g%c3%b6hler-k%c3%b6kpinar%20et%20al_final.pdf
File
MD5
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URL
https://hzi.openrepository.com/bitstream/10033/236989/8/g%c3%b6hler-k%c3%b6kpinar%20et%20al_final.pdf.txt
File
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göhler-kökpinar et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/2379352019-08-30T11:37:44Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Wei, Qing
author
Tarighi, Saeed
author
Dötsch, Andreas
author
Häussler, Susanne
author
Müsken, Mathias
author
Wright, Victoria J
author
Cámara, Miguel
author
Williams, Paul
author
Haenen, Steven
author
Boerjan, Bart
author
Bogaerts, Annelies
author
Vierstraete, Evy
author
Verleyen, Peter
author
Schoofs, Liliane
author
Willaert, Ronnie
author
De Groote, Valérie N
author
Michiels, Jan
author
Vercammen, Ken
author
Crabbé, Aurélie
author
Cornelis, Pierre
department
Research Group Microbiology, VIB Department of Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium.
2012-08-09T10:58:11Z
2011
Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV) of Pseudomonas aeruginosa. 2011, 6 (12):e29276 PLoS ONE
1932-6203
22195037
10.1371/journal.pone.0029276
http://hdl.handle.net/10033/237935
PloS one
Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.
en
Archived with thanks to PloS one
Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV) of Pseudomonas aeruginosa.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/237935/1/wei%20et%20al_final.pdf
File
MD5
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URL
https://hzi.openrepository.com/bitstream/10033/237935/8/wei%20et%20al_final.pdf.txt
File
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oai:repository.helmholtz-hzi.de:10033/2464432019-08-30T11:27:46Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Ferrer, Manuel
author
Ghazi, Azam
author
Beloqui, Ana
author
Vieites, José María
author
López-Cortés, Nieves
author
Marín-Navarro, Julia
author
Nechitaylo, Taras Y
author
Guazzaroni, María-Eugenia
author
Polaina, Julio
author
Waliczek, Agnes
author
Chernikova, Tatyana N
author
Reva, Oleg N
author
Golyshina, Olga V
author
Golyshin, Peter N
department
CSIC, Institute of Catalysis, Madrid, Spain. mferrer@icp.csic.es
2012-10-01T14:15:48Z
2012
Functional metagenomics unveils a multifunctional glycosyl hydrolase from the family 43 catalysing the breakdown of plant polymers in the calf rumen. 2012, 7 (6):e38134 PLoS ONE
1932-6203
22761666
10.1371/journal.pone.0038134
http://hdl.handle.net/10033/246443
PloS one
Microbial communities from cow rumen are known for their ability to degrade diverse plant polymers at high rates. In this work, we identified 15 hydrolases through an activity-centred metagenome analysis of a fibre-adherent microbial community from dairy cow rumen. Among them, 7 glycosyl hydrolases (GHs) and 1 feruloyl esterase were successfully cloned, expressed, purified and characterised. The most striking result was a protein of GH family 43 (GHF43), hereinafter designated as R_09-02, which had characteristics very distinct from the other proteins in this family with mono-functional β-xylosidase, α-xylanase, α-L-arabinase and α-L-arabinofuranosidase activities. R_09-02 is the first multifunctional enzyme to exhibit β-1,4 xylosidase, α-1,5 arabinofur(pyr)anosidase, β-1,4 lactase, α-1,6 raffinase, α-1,6 stachyase, β-galactosidase and α-1,4 glucosidase activities. The R_09-02 protein appears to originate from the chromosome of a member of Clostridia, a class of phylum Firmicutes, members of which are highly abundant in ruminal environment. The evolution of R_09-02 is suggested to be driven from the xylose- and arabinose-specific activities, typical for GHF43 members, toward a broader specificity to the glucose- and galactose-containing components of lignocellulose. The apparent capability of enzymes from the GHF43 family to utilise xylose-, arabinose-, glucose- and galactose-containing oligosaccharides has thus far been neglected by, or could not be predicted from, genome and metagenome sequencing data analyses. Taking into account the abundance of GHF43-encoding gene sequences in the rumen (up to 7% of all GH-genes) and the multifunctional phenotype herein described, our findings suggest that the ecological role of this GH family in the digestion of ligno-cellulosic matter should be significantly reconsidered.
en
Archived with thanks to PloS one
Functional metagenomics unveils a multifunctional glycosyl hydrolase from the family 43 catalysing the breakdown of plant polymers in the calf rumen.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/246443/1/Ferrer%20et%20al_final.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/2541172019-08-30T11:37:44Zcom_10033_6839col_10033_620726
Helmholtz Zentrum für Infektionsforschung Repository
author
Häussler, Susanne
author
Becker, Tanja
department
Department of Cell Biology, Helmholtz Center for Infection Research, Braunschweig, Germany. susanne.haeussler@helmholtz-hzi.de
2012-11-30T16:48:04Z
2008
The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas aeruginosa populations. 2008, 4 (9):e1000166 PLoS Pathog.
1553-7374
18818733
10.1371/journal.ppat.1000166
http://hdl.handle.net/10033/254117
PLoS pathogens
When environmental conditions deteriorate and become inhospitable, generic survival strategies for populations of bacteria may be to enter a dormant state that slows down metabolism, to develop a general tolerance to hostile parameters that characterize the habitat, and to impose a regime to eliminate damaged members. Here, we provide evidence that the pseudomonas quinolone signal (PQS) mediates induction of all of these phenotypes. For individual cells, PQS, an interbacterial signaling molecule of Pseudomonas aeruginosa, has both deleterious and beneficial activities: on the one hand, it acts as a pro-oxidant and sensitizes the bacteria towards oxidative and other stresses and, on the other, it efficiently induces a protective anti-oxidative stress response. We propose that this dual function fragments populations into less and more stress tolerant members which respond differentially to developing stresses in deteriorating habitats. This suggests that a little poison may be generically beneficial to populations, in promoting survival of the fittest, and in contributing to bacterial multi-cellular behavior. It further identifies PQS as an essential mediator of the shaping of the population structure of Pseudomonas and of its response to and survival in hostile environmental conditions.
en
Archived with thanks to PLoS pathogens
The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas aeruginosa populations.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/254117/1/H%c3%a4ussler%20and%20Becker_final.pdf
File
MD5
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URL
https://hzi.openrepository.com/bitstream/10033/254117/8/H%c3%a4ussler%20and%20Becker_final.pdf.txt
File
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oai:repository.helmholtz-hzi.de:10033/2640532019-08-30T11:28:51Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Del Pozo, Mercedes V
author
Fernández-Arrojo, Lucía
author
Gil-Martínez, Jorge
author
Montesinos, Alejandro
author
Chernikova, Tatyana N
author
Nechitaylo, Taras Y
author
Waliszek, Agnes
author
Tortajada, Marta
author
Rojas, Antonia
author
Huws, Sharon A
author
Golyshina, Olga V
author
Newbold, Charles J
author
Polaina, Julio
author
Ferrer, Manuel
author
Golyshin, Peter N
department
CSIC, Institute of Catalysis, 28049, Madrid, Spain. mferrer@icp.csic.es.
2013-01-03T11:30:51Z
2012
Microbial β-glucosidases from cow rumen metagenome enhance the saccharification of lignocellulose in combination with commercial cellulase cocktail. 2012, 5 (1):73 Biotechnol Biofuels
1754-6834
22998985
10.1186/1754-6834-5-73
http://hdl.handle.net/10033/264053
Biotechnology for biofuels
A complete saccharification of plant polymers is the critical step in the efficient production of bio-alcohols. Beta-glucosidases acting in the degradation of intermediate gluco-oligosaccharides produced by cellulases limit the yield of the final product.
en
Archived with thanks to Biotechnology for biofuels
Microbial β-glucosidases from cow rumen metagenome enhance the saccharification of lignocellulose in combination with commercial cellulase cocktail.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/264053/1/Del%20Pozo%20et%20al_final.pdf
File
MD5
1ac922ebf384df31c06226382db115b0
1341505
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Del Pozo et al_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/264053/8/Del%20Pozo%20et%20al_final.pdf.txt
File
MD5
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Del Pozo et al_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/2666342019-08-30T11:28:51Zcom_10033_6855com_10033_6839col_10033_6856
Helmholtz Zentrum für Infektionsforschung Repository
author
Kügler, Jonas
author
Schmelz, Stefan
author
Gentzsch, Juliane
author
Haid, Sibylle
author
Pollmann, Erik
author
van den Heuvel, Joop
author
Franke, Raimo
author
Pietschmann, Thomas
author
Heinz, Dirk W
author
Collins, John
department
Research Group Directed Evolution, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany.
2013-01-23T10:44:47Z
2012-11-09
High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease refractory to common resistant mutants. 2012, 287 (46):39224-32 J. Biol. Chem.
1083-351X
22965230
10.1074/jbc.M112.393843
http://hdl.handle.net/10033/266634
The Journal of biological chemistry
Hepatitis C virus (HCV) NS3-4A protease is essential for viral replication. All current small molecular weight drugs against NS3-4A are substrate peptidomimetics that have a similar binding and resistance profile. We developed inhibitory peptides (IPs) capping the active site and binding via a novel "tyrosine" finger at an alternative NS3-4A site that is of particular interest for further HCV drug development. The peptides are not cleaved due to a combination of geometrical constraints and impairment of the oxyanion hole function. Selection and optimization through combinatorial phagemid display, protein crystallography, and further modifications resulted in a 32-amino acid peptide with a K(i) of 0.53 nm. Inhibition of viral replication in cell culture was demonstrated by fusion to a cell-penetrating peptide. Negligible susceptibility to known (A156V and R155K) resistance mutations of the NS3-4A protease was observed. This work shows for the first time that antiviral peptides can target an intracellular site and reveals a novel druggable site on the HCV protease.
en
Archived with thanks to The Journal of biological chemistry
High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease refractory to common resistant mutants.
Article
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https://hzi.openrepository.com/bitstream/10033/266634/1/K%c3%bcgler%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/2837782019-08-30T11:30:58Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sass, Andrea M
author
McKew, Boyd A
author
Sass, Henrik
author
Fichtel, Jörg
author
Timmis, Kenneth N
author
McGenity, Terry J
department
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, UK. sassam@Cardiff.ac.uk
2013-04-24T13:57:09Z
2008
Diversity of Bacillus-like organisms isolated from deep-sea hypersaline anoxic sediments. 2008, 4:8 Saline Syst.
1746-1448
18541011
10.1186/1746-1448-4-8
http://hdl.handle.net/10033/283778
Saline systems
The deep-sea, hypersaline anoxic brine lakes in the Mediterranean are among the most extreme environments on earth, and in one of them, the MgCl2-rich Discovery basin, the presence of active microbes is equivocal. However, thriving microbial communities have been detected especially in the chemocline between deep seawater and three NaCl-rich brine lakes, l'Atalante, Bannock and Urania. By contrast, the microbiota of these brine-lake sediments remains largely unexplored.
en
Archived with thanks to Saline systems
Diversity of Bacillus-like organisms isolated from deep-sea hypersaline anoxic sediments.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/283778/1/Sass%20et%20al_final.pdf
File
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URL
https://hzi.openrepository.com/bitstream/10033/283778/8/Sass%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/2943262019-08-30T11:28:51Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Cavaletti, Linda
author
Monciardini, Paolo
author
Bamonte, Ruggiero
author
Schumann, Peter
author
Rohde, Manfred
author
Sosio, Margherita
author
Donadio, Stefano
department
Vicuron Pharmaceuticals, 21040 Gerenzano, Italy.
2013-06-21T10:22:40Z
2006-06
New lineage of filamentous, spore-forming, gram-positive bacteria from soil. 2006, 72 (6):4360-9 Appl. Environ. Microbiol.
0099-2240
16751552
10.1128/AEM.00132-06
http://hdl.handle.net/10033/294326
Applied and environmental microbiology
A novel bacterial strain that was isolated from an Italian soil and was designated SOSP1-21T forms branched mycelia in solid and liquid media and has a filamentous morphology similar to that of some genera belonging to the Actinobacteria. Electron microscopy showed that this organism has a grape-like appearance, resulting from interlacing of spores originating from sporophoric hyphae. Ten strains that are morphologically related to SOSP1-21T were recovered from soil. Phylogenetic analyses of 16S rRNA gene segments confirmed the relatedness of these strains to SOSP1-21T and indicated that the newly isolated strains form separate clades in a deeply branching lineage. The closest matches for the 16S rRNA sequences of all the strains (around 79% identity) were matches with representatives of the Chloroflexi, although the affiliation with this division was not supported by high bootstrap values. The strains are mesophilic aerobic heterotrophs and are also capable of growing under microaerophilic conditions. They all stain gram positive. Strain SOSP1-21T contains ornithine, alanine, glutamic acid, serine, and glycine as the peptidoglycan amino acids. In addition, an unusual level of C16:1 2OH (30%) was found in the cellular fatty acids. The G+C content of SOSP1-21T genomic DNA is 53.9%, and MK-9(H2) was the only menaquinone detected. All these data suggest that SOSP1-21T and the related strains may constitute a new division of filamentous, spore-forming, gram-positive bacteria. We propose the name Ktedobacter racemifer gen. nov., sp. nov. for strain SOSP1-21T.
en
Archived with thanks to Applied and environmental microbiology
New lineage of filamentous, spore-forming, gram-positive bacteria from soil.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/294326/8/Cavaletti%20et%20al_final.pdf
File
MD5
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URL
https://hzi.openrepository.com/bitstream/10033/294326/9/Cavaletti%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/2943252019-08-30T11:34:48Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Eichler, Stefan
author
Christen, Richard
author
Höltje, Claudia
author
Westphal, Petra
author
Bötel, Julia
author
Brettar, Ingrid
author
Mehling, Arndt
author
Höfle, Manfred G
department
Department of Environmental Microbiology, GBF-German Research Center for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
2013-06-21T09:25:47Z
2006-03
Composition and dynamics of bacterial communities of a drinking water supply system as assessed by RNA- and DNA-based 16S rRNA gene fingerprinting. 2006, 72 (3):1858-72 Appl. Environ. Microbiol.
0099-2240
16517632
10.1128/AEM.72.3.1858-1872.2006
http://hdl.handle.net/10033/294325
Applied and environmental microbiology
Bacterial community dynamics of a whole drinking water supply system (DWSS) were studied from source to tap. Raw water for this DWSS is provided by two reservoirs with different water characteristics in the Harz mountains of Northern Germany. Samples were taken after different steps of treatment of raw water (i.e., flocculation, sand filtration, and chlorination) and at different points along the supply system to the tap. RNA and DNA were extracted from the sampled water. The 16S rRNA or its genes were partially amplified by reverse transcription-PCR or PCR and analyzed by single-strand conformation polymorphism community fingerprints. The bacterial community structures of the raw water samples from the two reservoirs were very different, but no major changes of these structures occurred after flocculation and sand filtration. Chlorination of the processed raw water strongly affected bacterial community structure, as reflected by the RNA-based fingerprints. This effect was less pronounced for the DNA-based fingerprints. After chlorination, the bacterial community remained rather constant from the storage containers to the tap. Furthermore, the community structure of the tap water did not change substantially for several months. Community composition was assessed by sequencing of abundant bands and phylogenetic analysis of the sequences obtained. The taxonomic compositions of the bacterial communities from both reservoirs were very different at the species level due to their different limnologies. On the other hand, major taxonomic groups, well known to occur in freshwater, such as Alphaproteobacteria, Betaproteobacteria, and Bacteroidetes, were found in both reservoirs. Significant differences in the detection of the major groups were observed between DNA-based and RNA-based fingerprints irrespective of the reservoir. Chlorination of the drinking water seemed to promote growth of nitrifying bacteria. Detailed analysis of the community dynamics of the whole DWSS revealed a significant influence of both source waters on the overall composition of the drinking water microflora and demonstrated the relevance of the raw water microflora for the drinking water microflora provided to the end user.
en
Archived with thanks to Applied and environmental microbiology
Composition and dynamics of bacterial communities of a drinking water supply system as assessed by RNA- and DNA-based 16S rRNA gene fingerprinting.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/294325/8/Eichler%20et%20al_final.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/294325/10/Eichler%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/2943292019-08-30T11:33:57Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Labrenz, Matthias
author
Brettar, Ingrid
author
Christen, Richard
author
Flavier, Sebastien
author
Bötel, Julia
author
Höfle, Manfred G
department
Department of Environmental Microbiology, GBF-German Research Centre for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig, Germany.
2013-06-21T12:39:15Z
2004-08
Development and application of a real-time PCR approach for quantification of uncultured bacteria in the central Baltic Sea. 2004, 70 (8):4971-9 Appl. Environ. Microbiol.
0099-2240
15294837
10.1128/AEM.70.8.4971-4979.2004
http://hdl.handle.net/10033/294329
Applied and environmental microbiology
We have developed a highly sensitive approach to assess the abundance of uncultured bacteria in water samples from the central Baltic Sea by using a noncultured member of the "Epsilonproteobacteria" related to Thiomicrospira denitrificans as an example. Environmental seawater samples and samples enriched for the target taxon provided a unique opportunity to test the approach over a broad range of abundances. The approach is based on a combination of taxon- and domain-specific real-time PCR measurements determining the relative T. denitrificans-like 16S rRNA gene and 16S rRNA abundances, as well as the determination of total cell counts and environmental RNA content. It allowed quantification of T. denitrificans-like 16S rRNA molecules or 16S rRNA genes as well as calculation of the number of ribosomes per T. denitrificans-like cell. Every real-time measurement and its specific primer system were calibrated using environmental nucleic acids obtained from the original habitat for external standardization. These standards, as well as the respective samples to be measured, were prepared from the same DNA or RNA extract. Enrichment samples could be analyzed directly, whereas environmental templates had to be preamplified with general bacterial primers before quantification. Preamplification increased the sensitivity of the assay by more than 4 orders of magnitude. Quantification of enrichments with or without a preamplification step yielded comparable results. T. denitrificans-like 16S rRNA molecules ranged from 7.1 x 10(3) to 4.4 x 10(9) copies ml(-1) or 0.002 to 49.7% relative abundance. T. denitrificans-like 16S rRNA genes ranged from 9.0 x 10(1) to 2.2 x10(6) copies ml(-1) or 0.01 to 49.7% relative abundance. Detection limits of this real-time-PCR approach were 20 16S rRNA molecules or 0.2 16S rRNA gene ml(-1). The number of ribosomes per T. denitrificans-like cell was estimated to range from 20 to 200 in seawater and reached up to 2,000 in the enrichments. The results indicate that our real-time PCR approach can be used to determine cellular and relative abundances of uncultured marine bacterial taxa and to provide information about their levels of activity in their natural environment.
en
Archived with thanks to Applied and environmental microbiology
Development and application of a real-time PCR approach for quantification of uncultured bacteria in the central Baltic Sea.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/294329/6/Labrenz%20et%20al_final.pdf
File
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URL
https://hzi.openrepository.com/bitstream/10033/294329/9/Labrenz%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/2970562019-08-30T11:33:05Zcom_10033_311624com_10033_6839com_10033_311308com_10033_338554col_10033_621787col_10033_311625col_10033_620777
Helmholtz Zentrum für Infektionsforschung Repository
author
Khetarpal, Niyati
author
Poddar, Ankur
author
Nemani, Satish K
author
Dhar, Nisha
author
Patil, Aravind
author
Negi, Priyanka
author
Perween, Ashiya
author
Viswanathan, Ramaswamy
author
Lünsdorf, Heinrich
author
Tyagi, Poornima
author
Raut, Rajendra
author
Arora, Upasana
author
Jain, Swatantra K
author
Rinas, Ursula
author
Swaminathan, Sathyamangalam
author
Khanna, Navin
department
Recombinant Gene Products Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India. swami@icgeb.res.in.
2013-07-26T14:14:02Z
2013
Dengue-specific subviral nanoparticles: design, creation and characterization. 2013, 11 (1):15 J Nanobiotechnology
1477-3155
23706089
10.1186/1477-3155-11-15
http://hdl.handle.net/10033/297056
Journal of nanobiotechnology
Dengue is today the most significant of arboviral diseases. Novel tools are necessary to effectively address the problem of dengue. Virus-like particles (VLP) offer a versatile nanoscale platform for developing tools with potential biomedical applications. From the perspective of a potentially useful dengue-specific tool, the dengue virus envelope protein domain III (EDIII), endowed with serotype-specificity, host receptor recognition and the capacity to elicit virus-neutralizing antibodies, is an attractive candidate.
en
Archived with thanks to Journal of nanobiotechnology
Dengue-specific subviral nanoparticles: design, creation and characterization.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/297056/1/Khetarpal%20et%20al_final.pdf
File
MD5
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URL
https://hzi.openrepository.com/bitstream/10033/297056/8/Khetarpal%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/2995232019-08-30T11:35:13Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Kube, Michael
author
Chernikova, Tatyana N
author
Al-Ramahi, Yamal
author
Beloqui, Ana
author
Lopez-Cortez, Nieves
author
Guazzaroni, María-Eugenia
author
Heipieper, Hermann J
author
Klages, Sven
author
Kotsyurbenko, Oleg R
author
Langer, Ines
author
Nechitaylo, Taras Y
author
Lünsdorf, Heinrich
author
Fernández, Marisol
author
Juárez, Silvia
author
Ciordia, Sergio
author
Singer, Alexander
author
Kagan, Olga
author
Egorova, Olga
author
Alain Petit, Pierre
author
Stogios, Peter
author
Kim, Youngchang
author
Tchigvintsev, Anatoli
author
Flick, Robert
author
Denaro, Renata
author
Genovese, Maria
author
Albar, Juan P
author
Reva, Oleg N
author
Martínez-Gomariz, Montserrat
author
Tran, Hai
author
Ferrer, Manuel
author
Savchenko, Alexei
author
Yakunin, Alexander F
author
Yakimov, Michail M
author
Golyshina, Olga V
author
Reinhardt, Richard
author
Golyshin, Peter N
department
1] Max-Planck Institute for Molecular Genetics, Berlin-Dahlem D-14195, Germany [2] Section Phytomedicine, Department of Crop and Animal Sciences, Humboldt-Universität zu Berlin, Berlin-Dahlem D-14195, Germany.
2013-08-22T14:07:55Z
2013-07-23
Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica. 2013, 4:2156 Nat Commun
2041-1723
23877221
10.1038/ncomms3156
http://hdl.handle.net/10033/299523
Nature communications
Ubiquitous bacteria from the genus Oleispira drive oil degradation in the largest environment on Earth, the cold and deep sea. Here we report the genome sequence of Oleispira antarctica and show that compared with Alcanivorax borkumensis-the paradigm of mesophilic hydrocarbonoclastic bacteria-O. antarctica has a larger genome that has witnessed massive gene-transfer events. We identify an array of alkane monooxygenases, osmoprotectants, siderophores and micronutrient-scavenging pathways. We also show that at low temperatures, the main protein-folding machine Cpn60 functions as a single heptameric barrel that uses larger proteins as substrates compared with the classical double-barrel structure observed at higher temperatures. With 11 protein crystal structures, we further report the largest set of structures from one psychrotolerant organism. The most common structural feature is an increased content of surface-exposed negatively charged residues compared to their mesophilic counterparts. Our findings are relevant in the context of microbial cold-adaptation mechanisms and the development of strategies for oil-spill mitigation in cold environments.
en
Archived with thanks to Nature communications
Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/299523/1/Kube%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/3037682019-08-30T11:37:00Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Dammeyer, Thorben
author
Timmis, Kenneth N
author
Tinnefeld, Philip
department
Institut für Physikalische und Theoretische Chemie, NanoBioSciences, Technische Universität Braunschweig, Hans Sommer Str, 10, Braunschweig 38106, Germany. T.Dammeyer@tu-braunschweig.de
2013-10-22T09:32:58Z
2013
Broad host range vectors for expression of proteins with (Twin-) Strep-tag, His-tag and engineered, export optimized yellow fluorescent protein. 2013, 12:49 Microb. Cell Fact.
1475-2859
23687945
10.1186/1475-2859-12-49
http://hdl.handle.net/10033/303768
Microbial cell factories
In current protein research, a limitation still is the production of active recombinant proteins or native protein associations to assess their function. Especially the localization and analysis of protein-complexes or the identification of modifications and small molecule interaction partners by co-purification experiments requires a controllable expression of affinity- and/or fluorescence tagged variants of a protein of interest in its native cellular background. Advantages of periplasmic and/or homologous expressions can frequently not be realized due to a lack of suitable tools. Instead, experiments are often limited to the heterologous production in one of the few well established expression strains.
en
Archived with thanks to Microbial cell factories
Broad host range vectors for expression of proteins with (Twin-) Strep-tag, His-tag and engineered, export optimized yellow fluorescent protein.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/303768/1/Dammeyer%2c%20Timmis%20and%20Tinnefeld_final.pdf
File
MD5
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Dammeyer, Timmis and Tinnefeld_final.pdf
URL
https://hzi.openrepository.com/bitstream/10033/303768/8/Dammeyer%2c%20Timmis%20and%20Tinnefeld_final.pdf.txt
File
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Dammeyer, Timmis and Tinnefeld_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/3116262019-08-30T11:27:16Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Lang, Elke
author
Reichenbach, Hans
department
Leibniz-Institut DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstrasse 7B, 38124 Braunschweig, Germany
2014-01-20T15:13:11Z
2013-11
Designation of type strains for seven species of the order Myxococcales and proposal for neotype strains of Cystobacter ferrugineus, Cystobacter minus and Polyangium fumosum. 2013, 63 (Pt 11):4354-60 Int. J. Syst. Evol. Microbiol.
1466-5034
24187023
10.1099/ijs.0.056440-0
http://hdl.handle.net/10033/311626
International journal of systematic and evolutionary microbiology
Ten species of the order Myxococcales with validly published names are devoid of living type strains. Four species of the genus Chondromyces are represented by dead herbarium samples as the type material. For a species of the genus Melittangium and two species of the genus Polyangium, no physical type material was assigned at the time of validation of the names or later on. In accordance with rule 18f of the International Code of Nomenclature of Bacteria the following type strains are designated for these species: strain Cm a14(T) ( = DSM 14605(T) = JCM 12615(T)) as the type strain of Chondromyces apiculatus, strain Cm c5(T) ( = DSM 14714(T) = JCM 12616(T)) as the type strain of Chondromyces crocatus, strain Sy t2(T) ( = DSM 14631(T) = JCM 12617(T)) as the type strain of Chondromyces lanuginosus, strain Cm p51(T) ( = DSM 14607(T) = JCM 12618(T)) as the type strain of Chondromyces pediculatus, strain Me b8(T) ( = DSM 14713(T) = JCM 12633(T)) as the type strain of Melittangium boletus, strain Pl s12(T) ( = DSM 14670(T) = JCM 12637(T)) as the type strain of Polyangium sorediatum and strain Pl sm5(T) ( = DSM 14734(T) = JCM 12638(T)) as the type strain of Polyangium spumosum. Furthermore, the type strains given for three species of the genera Cystobacter and Polyangium had been kept at one university institute and have been lost according to our investigations. In accordance with Rule 18c of the Bacteriological Code, we propose the following neotype strains: strain Cb fe18 ( = DSM 14716 = JCM 12624) as the neotype strain of Cystobacter ferrugineus, strain Cb m2 ( = DSM 14751 = JCM 12627) as the neotype strain of Cystobacter minus and strain Pl fu5 ( = DSM 14668 = JCM 12636) as the neotype strain of Polyangium fumosum. The proposals of the strains are based on the descriptions and strain proposals given in the respective chapters of Bergey's Manual of Systematic Bacteriology (2005).
en
Archived with thanks to International journal of systematic and evolutionary microbiology
Designation of type strains for seven species of the order Myxococcales and proposal for neotype strains of Cystobacter ferrugineus, Cystobacter minus and Polyangium fumosum.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/311626/1/Lang%20und%20Reichenbach_final.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/311626/2/Supplementary%20Table%20.pdf
File
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URL
https://hzi.openrepository.com/bitstream/10033/311626/11/Lang%20und%20Reichenbach_final.pdf.txt
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Lang und Reichenbach_final.pdf.txt
URL
https://hzi.openrepository.com/bitstream/10033/311626/12/Supplementary%20Table%20.pdf.txt
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Supplementary Table .pdf.txt
oai:repository.helmholtz-hzi.de:10033/3137182019-08-30T11:30:53Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Arias, Sagrario
author
Bassas-Galia, Monica
author
Molinari, Gabriella
author
Timmis, Kenneth N.
department
Environmental microbiology; Helmholtz Centre for infection research; Inhoffenstr. 7, D-38124 Braunschweig, Germany
2014-03-06T10:10:50Z
2014-03-06
Tight coupling of polymerization and depolymerization of polyhydroxyalkanoates ensures efficient management of carbon resources in Pseudomonas putida 2013, 6 (5):551 Microbial Biotechnology
17517915
10.1111/1751-7915.12040
http://hdl.handle.net/10033/313718
Microbial Biotechnology
Archived with thanks to Microbial Biotechnology
Tight coupling of polymerization and depolymerization of polyhydroxyalkanoates ensures efficient management of carbon resources in Pseudomonas putida
Article
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URL
https://hzi.openrepository.com/bitstream/10033/313718/1/Arias%20et%20al_final.pdf
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https://hzi.openrepository.com/bitstream/10033/313718/8/Arias%20et%20al_final.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/3464082019-08-30T11:31:23Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Esatbeyoglu, Tuba
author
Wray, Victor
author
Winterhalter, Peter
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2015-03-09T13:51:17Z
2015-07-15
Isolation of dimeric, trimeric, tetrameric and pentameric procyanidins from unroasted cocoa beans (Theobroma cacao L.) using countercurrent chromatography. 2015, 179:278-89 Food Chem
0308-8146
25722166
10.1016/j.foodchem.2015.01.130
http://hdl.handle.net/10033/346408
Food chemistry
The main procyanidins, including dimeric B2 and B5, trimeric C1, tetrameric and pentameric procyanidins, were isolated from unroasted cocoa beans (Theobroma cacao L.) using various techniques of countercurrent chromatography, such as high-speed countercurrent chromatography (HSCCC), low-speed rotary countercurrent chromatography (LSRCCC) and spiral-coil LSRCCC. Furthermore, dimeric procyanidins B1 and B7, which are not present naturally in the analysed cocoa beans, were obtained after semisynthesis of cocoa bean polymers with (+)-catechin as nucleophile and separated by countercurrent chromatography. In this way, the isolation of dimeric procyanidin B1 in considerable amounts (500mg, purity>97%) was possible in a single run. This is the first report concerning the isolation and semisynthesis of dimeric to pentameric procyanidins from T. cacao by countercurrent chromatography. Additionally, the chemical structures of tetrameric (cinnamtannin A2) and pentameric procyanidins (cinnamtannin A3) were elucidated on the basis of (1)H NMR spectroscopy. Interflavanoid linkage was determined by NOE-correlations, for the first time.
en
Isolation of dimeric, trimeric, tetrameric and pentameric procyanidins from unroasted cocoa beans (Theobroma cacao L.) using countercurrent chromatography.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/346408/1/Esatbeyoglu%2c%20Wray%20and%20Winterhalter_final.pdf
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https://hzi.openrepository.com/bitstream/10033/346408/2/Esatbeyoglu2015_cocoaSuppl.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/346408/12/Esatbeyoglu2015_cocoaSuppl.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/5588392019-08-30T11:29:17Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Rasch, Janine
author
Theuerkorn, Martin
author
Ünal, Can
author
Heinsohn, Natascha
author
Tran, Stefan
author
Fischer, Gunter
author
Weiwad, Matthias
author
Steinert, Michael
department
Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
2015-07-03T12:55:09Z
2015
Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit Specific Antimicrobial Activity Against Legionella pneumophila. 2015, 3:41 Front Bioeng Biotechnol
2296-4185
25870856
10.3389/fbioe.2015.00041
http://hdl.handle.net/10033/558839
Frontiers in bioengineering and biotechnology
Macrophage infectivity potentiator (Mip) and Mip-like proteins are virulence factors in a wide range of pathogens including Legionella pneumophila. These proteins belong to the FK506 binding protein (FKBP) family of peptidyl-prolyl-cis/trans-isomerases (PPIases). In L. pneumophila, the PPIase activity of Mip is required for invasion of macrophages, transmigration through an in vitro lung-epithelial barrier, and full virulence in the guinea pig infection model. Additionally, Mip is a moonlighting protein that binds to collagen IV in the extracellular matrix. Here, we describe the development and synthesis of cycloheximide derivatives with adamantyl moieties as novel FKBP ligands, and analyze their effect on the viability of L. pneumophila and other bacteria. All compounds efficiently inhibited PPIase activity of the prototypic human FKBP12 as well as Mip with IC50-values as low as 180 nM and 1.7 μM, respectively. Five of these derivatives inhibited the growth of L. pneumophila at concentrations of 30-40 μM, but exhibited no effect on other tested bacterial species indicating a specific spectrum of antibacterial activity. The derivatives carrying a 3,5-dimethyladamantan-1-[yl]acetamide substitution (MT_30.32), and a 3-ethyladamantan-1-[yl]acetamide substitution (MT_30.51) had the strongest effects in PPIase- and liquid growth assays. MT_30.32 and MT_30.51 were also inhibitory in macrophage infection studies without being cytotoxic. Accordingly, by applying a combinatorial approach, we were able to generate novel, hybrid inhibitors consisting of cycloheximide and adamantane, two known FKBP inhibitors that interact with different parts of the PPIase domain, respectively. Interestingly, despite the proven Mip-inhibitory activity, the viability of a Mip-deficient strain was affected to the same degree as its wild type. Hence, we also propose that cycloheximide derivatives with adamantyl moieties are potent PPIase inhibitors with multiple targets in L. pneumophila.
en
Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit Specific Antimicrobial Activity Against Legionella pneumophila.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/558839/1/Rasch%20et%20al_final.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/558839/8/Rasch%20et%20al_final.pdf.txt
File
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oai:repository.helmholtz-hzi.de:10033/5588272019-08-30T11:27:16Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Xiong, Qiuhong
author
Ünal, Can
author
Matthias, Jan
author
Steinert, Michael
author
Eichinger, Ludwig
department
Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
2015-07-03T13:49:35Z
2015-04
The phenotypes of ATG9, ATG16 and ATG9/16 knock-out mutants imply autophagy-dependent and -independent functions. 2015, 5 (4):150008 Open Biol
2046-2441
25878144
10.1098/rsob.150008
http://hdl.handle.net/10033/558827
Open biology
Macroautophagy is a highly conserved intracellular bulk degradation system of all eukaryotic cells. It is governed by a large number of autophagy proteins (ATGs) and is crucial for many cellular processes. Here, we describe the phenotypes of Dictyostelium discoideum ATG16(-) and ATG9(-)/16(-) cells and compare them to the previously reported ATG9(-) mutant. ATG16 deficiency caused an increase in the expression of several core autophagy genes, among them atg9 and the two atg8 paralogues. The single and double ATG9 and ATG16 knock-out mutants had complex phenotypes and displayed severe and comparable defects in pinocytosis and phagocytosis. Uptake of Legionella pneumophila was reduced. In addition, ATG9(-) and ATG16(-) cells had dramatic defects in autophagy, development and proteasomal activity which were much more severe in the ATG9(-)/16(-) double mutant. Mutant cells showed an increase in poly-ubiquitinated proteins and contained large ubiquitin-positive protein aggregates which partially co-localized with ATG16-GFP in ATG9(-)/16(-) cells. The more severe autophagic, developmental and proteasomal phenotypes of ATG9(-)/16(-) cells imply that ATG9 and ATG16 probably function in parallel in autophagy and have in addition autophagy-independent functions in further cellular processes.
en
The phenotypes of ATG9, ATG16 and ATG9/16 knock-out mutants imply autophagy-dependent and -independent functions.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/558827/1/Xiong%20et%20al_final.pdf
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oai:repository.helmholtz-hzi.de:10033/6207612019-08-30T11:34:48Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Dammeyer, Thorben
author
Timmis, Kenneth N
author
Tinnefeld, Philip
2017-01-27T08:57:48Z
2013-05-20
Microbial Cell Factories. 2013 May 20;12(1):49
http://dx.doi.org/10.1186/1475-2859-12-49
Abstract Background In current protein research, a limitation still is the production of active recombinant proteins or native protein associations to assess their function. Especially the localization and analysis of protein-complexes or the identification of modifications and small molecule interaction partners by co-purification experiments requires a controllable expression of affinity- and/or fluorescence tagged variants of a protein of interest in its native cellular background. Advantages of periplasmic and/or homologous expressions can frequently not be realized due to a lack of suitable tools. Instead, experiments are often limited to the heterologous production in one of the few well established expression strains. Results Here, we introduce a series of new RK2 based broad host range expression plasmids for inducible production of affinity- and fluorescence tagged proteins in the cytoplasm and periplasm of a wide range of Gram negative hosts which are designed to match the recently suggested modular Standard European Vector Architecture and database. The vectors are equipped with a yellow fluorescent protein variant which is engineered to fold and brightly fluoresce in the bacterial periplasm following Sec-mediated export, as shown from fractionation and imaging studies. Expression of Strep-tag®II and Twin-Strep-tag® fusion proteins in Pseudomonas putida KT2440 is demonstrated for various ORFs. Conclusion The broad host range constructs we have produced enable good and controlled expression of affinity tagged protein variants for single-step purification and qualify for complex co-purification experiments. Periplasmic export variants enable production of affinity tagged proteins and generation of fusion proteins with a novel engineered Aequorea-based yellow fluorescent reporter protein variant with activity in the periplasm of the tested Gram-negative model bacteria Pseudomonas putida KT2440 and Escherichia coli K12 for production, localization or co-localization studies. In addition, the new tools facilitate metabolic engineering and yield assessment for cytoplasmic or periplasmic protein production in a number of different expression hosts when yields in one initially selected are insufficient.
en
Broad host range vectors for expression of proteins with (Twin-) Strep-tag, His-tag and engineered, export optimized yellow fluorescent protein
Journal Article
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URL
https://hzi.openrepository.com/bitstream/10033/620761/1/12934_2013_Article_846.pdf
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oai:repository.helmholtz-hzi.de:10033/6207032019-08-30T11:26:13Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Del Pozo, Mercedes V
author
Fernández-Arrojo, Lucía
author
Gil-Martínez, Jorge
author
Montesinos, Alejandro
author
Chernikova, Tatyana N
author
Nechitaylo, Taras Y
author
Waliszek, Agnes
author
Tortajada, Marta
author
Rojas, Antonia
author
Huws, Sharon A
author
Golyshina, Olga V
author
Newbold, Charles J
author
Polaina, Julio
author
Ferrer, Manuel
author
Golyshin, Peter N
2017-01-16T15:28:06Z
2012-09-21
Biotechnology for Biofuels. 2012 Sep 21;5(1):73
http://dx.doi.org/10.1186/1754-6834-5-73
Abstract Background A complete saccharification of plant polymers is the critical step in the efficient production of bio-alcohols. Beta-glucosidases acting in the degradation of intermediate gluco-oligosaccharides produced by cellulases limit the yield of the final product. Results In the present work, we have identified and then successfully cloned, expressed, purified and characterised 4 highly active beta-glucosidases from fibre-adherent microbial community from the cow rumen. The enzymes were most active at temperatures 45–55°C and pH 4.0-7.0 and exhibited high affinity and activity towards synthetic substrates such as p-nitrophenyl-beta-D-glucopyranoside (pNPbetaG) and pNP-beta-cellobiose, as well as to natural cello-oligosaccharides ranging from cellobiose to cellopentaose. The apparent capability of the most active beta-glucosidase, herein named LAB25g2, was tested for its ability to improve, at low dosage (31.25 units g-1 dry biomass, using pNPbetaG as substrate), the hydrolysis of pre-treated corn stover (dry matter content of 20%; 350 g glucan kg-1 dry biomass) in combination with a beta-glucosidase-deficient commercial Trichoderma reseei cellulase cocktail (5 units g-1 dry biomass in the basis of pNPbetaG). LAB25g2 increased the final hydrolysis yield by a factor of 20% (44.5 ± 1.7% vs. 34.5 ± 1.5% in control conditions) after 96–120 h as compared to control reactions in its absence or in the presence of other commercial beta-glucosidase preparations. The high stability (half-life higher than 5 days at 50°C and pH 5.2) and 2–38000 fold higher (as compared with reported beta-glucosidases) activity towards cello-oligosaccharides may account for its performance in supplementation assays. Conclusions The results suggest that beta-glucosidases from yet uncultured bacteria from animal digestomes may be of a potential interest for biotechnological processes related to the effective bio-ethanol production in combination with low dosage of commercial cellulases.
en
Microbial β-glucosidases from cow rumen metagenome enhance the saccharification of lignocellulose in combination with commercial cellulase cocktail
Journal Article
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URL
https://hzi.openrepository.com/bitstream/10033/620703/1/13068_2012_Article_187.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/5840772019-08-30T11:34:48Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Ünal, Can M
author
Steinert, Michael
department
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2015-12-17T12:51:09Z
2015-10
FKBPs in bacterial infections. 2015, 1850 (10):2096-102 Biochim. Biophys. Acta
0006-3002
25529296
10.1016/j.bbagen.2014.12.018
http://hdl.handle.net/10033/584077
Biochimica et biophysica acta
FK506-binding proteins (FKBPs) contain a domain with peptidyl-prolyl-cis/trans-isomerase (PPIase) activity and bind the immunosuppressive drugs FK506 and rapamycin. FKBPs belong to the immunophilin family and are found in eukaryotes and bacteria.
en
FKBPs in bacterial infections.
Article
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oai:repository.helmholtz-hzi.de:10033/5944092019-08-30T11:36:33Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Dammeyer, Thorben
author
Steinwand, Miriam
author
Krüger, Sarah-C
author
Dübel, Stefan
author
Hust, Michael
author
Timmis, Kenneth N
department
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2016-01-20T14:30:25Z
2011
Efficient production of soluble recombinant single chain Fv fragments by a Pseudomonas putida strain KT2440 cell factory. 2011, 10:11 Microb. Cell Fact.
1475-2859
21338491
10.1186/1475-2859-10-11
http://hdl.handle.net/10033/594409
Microbial cell factories
Recombinant antibody fragments have a wide range of applications in research, diagnostics and therapy. For many of these, small fragments like single chain fragment variables (scFv) function well and can be produced inexpensively in bacterial expression systems. Although Escherichia coli K-12 production systems are convenient, yields of different fragments, even those produced from codon-optimized expression systems, vary significantly. Where yields are inadequate, alternative production systems are needed. Pseudomonas putida strain KT2440 is a versatile biosafety strain known for good expression of heterologous genes, so we have explored its utility as a cell factory for production of scFvs.
en
Efficient production of soluble recombinant single chain Fv fragments by a Pseudomonas putida strain KT2440 cell factory.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/594409/1/Dammeyer%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/5992772019-08-30T11:37:23Zcom_10033_6853com_10033_6839col_10033_6854
Helmholtz Zentrum für Infektionsforschung Repository
author
Sabirova, Julia S
author
Haddouche, R
author
Van Bogaert, I N
author
Mulaa, F
author
Verstraete, W
author
Timmis, K N
author
Schmidt-Dannert, C
author
Nicaud, J M
author
Soetaert, W
department
Gesellschaft für biotechnologische Forschung (GBF), Mascheroder Weg 1, D-38124 Braunschweig, >Germany.
2016-02-26T10:49:07Z
2011-01
The 'LipoYeasts' project: using the oleaginous yeast Yarrowia lipolytica in combination with specific bacterial genes for the bioconversion of lipids, fats and oils into high-value products. 2011, 4 (1):47-54 Microb Biotechnol
1751-7915
21255371
10.1111/j.1751-7915.2010.00187.x
http://hdl.handle.net/10033/599277
Microbial biotechnology
The oleochemical industry is currently still dominated by conventional chemistry, with biotechnology only starting to play a more prominent role, primarily with respect to the biosurfactants or lipases, e.g. as detergents, or for biofuel production. A major bottleneck for all further biotechnological applications is the problem of the initial mobilization of cheap and vastly available lipid and oil substrates, which are then to be transformed into high-value biotechnological, nutritional or pharmacological products. Under the EU-sponsored LipoYeasts project we are developing the oleaginous yeast Yarrowia lipolytica into a versatile and high-throughput microbial factory that, by use of specific enzymatic pathways from hydrocarbonoclastic bacteria, efficiently mobilizes lipids by directing its versatile lipid metabolism towards the production of industrially valuable lipid-derived compounds like wax esters (WE), isoprenoid-derived compounds (carotenoids, polyenic carotenoid ester), polyhydroxyalkanoates (PHAs) and free hydroxylated fatty acids (HFAs). Different lipid stocks (petroleum, alkane, vegetable oil, fatty acid) and combinations thereof are being assessed as substrates in combination with different mutant and recombinant strains of Y. lipolytica, in order to modulate the composition and yields of the produced added-value products.
en
openAccess
The 'LipoYeasts' project: using the oleaginous yeast Yarrowia lipolytica in combination with specific bacterial genes for the bioconversion of lipids, fats and oils into high-value products.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/599277/1/Sabirova%20et%20al.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/6138722019-08-30T11:33:30Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Rueda, Fabián
author
Céspedes, María Virtudes
author
Sánchez-Chardi, Alejandro
author
Seras-Franzoso, Joaquin
author
Pesarrodona, Mireia
author
Ferrer-Miralles, Neus
author
Vázquez, Esther
author
Rinas, Ursula
author
Unzueta, Ugutz
author
Mamat, Uwe
author
Mangues, Ramón
author
García-Fruitós, Elena
author
Villaverde, Antonio
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-06-21T14:12:13Z
2016
Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli. 2016, 15 (1):59 Microb. Cell Fact.
1475-2859
27059706
10.1186/s12934-016-0457-z
http://hdl.handle.net/10033/613872
Microbial cell factories
Production of recombinant drugs in process-friendly endotoxin-free bacterial factories targets to a lessened complexity of the purification process combined with minimized biological hazards during product application. The development of nanostructured recombinant materials in innovative nanomedical activities expands such a need beyond plain functional polypeptides to complex protein assemblies. While Escherichia coli has been recently modified for the production of endotoxin-free proteins, no data has been so far recorded regarding how the system performs in the fabrication of smart nanostructured materials.
en
Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/6208562019-08-30T11:31:23Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Schmid, Ursula
author
Stenzel, Werner
author
Koschel, Josephin
author
Raptaki, Maria
author
Wang, Xu
author
Naumann, Michael
author
Matuschewski, Kai
author
Schlüter, Dirk
author
Nishanth, Gopala
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-03-13T10:39:04Z
2017
The Deubiquitinating Enzyme Cylindromatosis Dampens CD8(+) T Cell Responses and Is a Critical Factor for Experimental Cerebral Malaria and Blood-Brain Barrier Damage. 2017, 8:27 Front Immunol
28203236
10.3389/fimmu.2017.00027
http://hdl.handle.net/10033/620856
Frontiers in immunology
Cerebral malaria is a severe complication of human malaria and may lead to death of Plasmodium falciparum-infected individuals. Cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. Although CD8(+) T cells have been implicated in the development of murine experimental cerebral malaria (ECM), several other studies have shown that CD8(+) T cells confer protection against blood-stage infections. Since the role of host deubiquitinating enzymes (DUBs) in malaria is yet unknown, we investigated how the DUB cylindromatosis (CYLD), an important inhibitor of several cellular signaling pathways, influences the outcome of ECM. Upon infection with Plasmodium berghei ANKA (PbA) sporozoites or PbA-infected red blood cells, at least 90% of Cyld(-/-) mice survived the infection, whereas all congenic C57BL/6 mice displayed signatures of ECM, impaired parasite control, and disruption of the blood-brain barrier integrity. Cyld deficiency prevented brain pathology, including hemorrhagic lesions, enhanced activation of astrocytes and microglia, infiltration of CD8(+) T cells, and apoptosis of endothelial cells. Furthermore, PbA-specific CD8(+) T cell responses were augmented in the blood of Cyld(-/-) mice with increased production of interferon-γ and granzyme B and elevated activation of protein kinase C-θ and nuclear factor "kappa light-chain enhancer" of activated B cells. Importantly, accumulation of CD8(+) T cells in the brain of Cyld(-/-) mice was significantly reduced compared to C57BL/6 mice. Bone marrow chimera experiments showed that the absence of ECM signatures in infected Cyld(-/-) mice could be attributed to hematopoietic and radioresistant parenchymal cells, most likely endothelial cells that did not undergo apoptosis. Together, we were able to show that host deubiqutinating enzymes play an important role in ECM and that CYLD promotes ECM supporting it as a potential therapeutic target for adjunct therapy to prevent cerebral complications of severe malaria.
en
The Deubiquitinating Enzyme Cylindromatosis Dampens CD8(+) T Cell Responses and Is a Critical Factor for Experimental Cerebral Malaria and Blood-Brain Barrier Damage.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620856/1/Schmid%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6208942019-08-30T11:37:23Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Hoppe, Julia
author
Ünal, Can M
author
Thiem, Stefanie
author
Grimpe, Louisa
author
Goldmann, Torsten
author
Gaßler, Nikolaus
author
Richter, Matthias
author
Shevchuk, Olga
author
Steinert, Michael
department
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-04-12T14:12:57Z
2017
PilY1 Promotes Legionella pneumophila Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility. 2017, 7:63 Front Cell Infect Microbiol
2235-2988
28326293
10.3389/fcimb.2017.00063
http://hdl.handle.net/10033/620894
Frontiers in cellular and infection microbiology
Legionnaires' disease is an acute fibrinopurulent pneumonia. During infection Legionella pneumophila adheres to the alveolar lining and replicates intracellularly within recruited macrophages. Here we provide a sequence and domain composition analysis of the L. pneumophila PilY1 protein, which has a high homology to PilY1 of Pseudomonas aeruginosa. PilY1 proteins of both pathogens contain a von Willebrand factor A (vWFa) and a C-terminal PilY domain. Using cellular fractionation, we assigned the L. pneumophila PilY1 as an outer membrane protein that is only expressed during the transmissive stationary growth phase. PilY1 contributes to infection of human lung tissue explants (HLTEs). A detailed analysis using THP-1 macrophages and A549 lung epithelial cells revealed that this contribution is due to multiple effects depending on host cell type. Deletion of PilY1 resulted in a lower replication rate in THP-1 macrophages but not in A549 cells. Further on, adhesion to THP-1 macrophages and A549 epithelial cells was decreased. Additionally, the invasion into non-phagocytic A549 epithelial cells was drastically reduced when PilY1 was absent. Complementation variants of a PilY1-negative mutant revealed that the C-terminal PilY domain is essential for restoring the wild type phenotype in adhesion, while the putatively mechanosensitive vWFa domain facilitates invasion into non-phagocytic cells. Since PilY1 also promotes twitching motility of L. pneumophila, we discuss the putative contribution of this newly described virulence factor for bacterial dissemination within infected lung tissue.
en
PilY1 Promotes Legionella pneumophila Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620894/1/Hoppe%20et%20al.pdf
File
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URL
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oai:repository.helmholtz-hzi.de:10033/6209302019-08-30T11:29:47Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Just, Sissy
author
Nishanth, Gopala
author
Buchbinder, Jörn H
author
Wang, Xu
author
Naumann, Michael
author
Lavrik, Inna
author
Schlüter, Dirk
department
Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany.
2017-05-31T14:08:08Z
2016-12-22
A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection. 2016, 6:39796 Sci Rep
2045-2322
28004776
10.1038/srep39796
http://hdl.handle.net/10033/620930
Scientific reports
The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8(+) T cells but augments the proliferation of autoimmune CD4(+) T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20(fl/fl)) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8(+) T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8(+) T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8(+) T cells. In contrast, the primary CD4(+) T cell response was A20-independent. Upon secondary infection, the increase and function of pathogen-specific CD8(+) T cells, as well as pathogen control were significantly impaired in CD4-Cre A20(fl/fl) mice. In vitro, apoptosis and necroptosis of Listeria-specific A20-deficient CD8(+) T cells were strongly induced as demonstrated by increased caspase-3/7 activity, RIPK1/RIPK3 complex formation and more morphologically apoptotic and necroptotic CD8(+) T cells. In vitro, A20 limited CD95L and TNF-induced caspase3/7 activation. In conclusion, T cell-specific A20 limited the expansion but reduced apoptosis and necroptosis of Listeria-specific CD8(+) T cells, resulting in an impaired pathogen control in primary but improved clearance in secondary infection.
en
A20 Curtails Primary but Augments Secondary CD8(+) T Cell Responses in Intracellular Bacterial Infection.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620930/1/Just%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6209722019-08-30T11:32:16Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Muruganandam, Gopinath
author
Raasakka, Arne
author
Myllykoski, Matti
author
Kursula, Inari
author
Kursula, Petri
department
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-06-21T14:46:09Z
2017-05-16
Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase. 2017, 18 (1):7 BMC Biochem.
1471-2091
28511668
10.1186/s12858-017-0084-2
http://hdl.handle.net/10033/620972
BMC biochemistry
Eukaryotic tRNA splicing is an essential process in the transformation of a primary tRNA transcript into a mature functional tRNA molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that catalyze tRNA healing in yeast and higher eukaryotes are homologous to the members of the 2H phosphoesterase superfamily, in particular to the vertebrate myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase).
en
Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620972/1/Muruganandam%20et%20al.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/6209802019-08-30T11:33:29Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Lim, Michelle C C
author
Maubach, Gunter
author
Sokolova, Olga
author
Feige, Michael H
author
Diezko, Rolf
author
Buchbinder, Jörn
author
Backert, Steffen
author
Schlüter, Dirk
author
Lavrik, Inna N
author
Naumann, Michael
department
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-06-26T13:27:52Z
2017-06-02
Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death. 2017 Cell Death Differ.
1476-5403
28574503
10.1038/cdd.2017.89
http://hdl.handle.net/10033/620980
Cell death and differentiation
The human pathogen Helicobacter pylori infects more than half of the world's population and is a paradigm for persistent yet asymptomatic infection but increases the risk for chronic gastritis and gastric adenocarcinoma. For successful colonization, H. pylori needs to subvert the host cell death response, which serves to confine pathogen infection by killing infected cells and preventing malignant transformation. Infection of gastric epithelial cells by H. pylori provokes direct and fast activation of the proinflammatory and survival factor NF-κB, which regulates target genes, such as CXCL8, BIRC3 and TNFAIP3. However, it is not known how H. pylori exploits NF-κB activation and suppresses the inflammatory response and host apoptotic cell death, in order to avert the innate immune response and avoid cell loss, and thereby enhance colonization to establish long-term infection. Here we assign for the first time that H. pylori and also Campylobacter jejuni-induced ubiquitin-editing enzyme A20 bifunctionally terminates NF-κB activity and negatively regulates apoptotic cell death. Mechanistically, we show that the deubiquitinylase activity of A20 counteracts cullin3-mediated K63-linked ubiquitinylation of procaspase-8, therefore restricting the activity of caspase-8. Interestingly, another inducible NF-κB target gene, the scaffold protein p62, ameliorates the interaction of A20 with procaspase-8. In conclusion, pathogen-induced de novo synthesis of A20 regulates the shut-off of the survival factor NF-κB but, on the other hand, also impedes caspase-8-dependent apoptotic cell death so as to promote the persistence of pathogens.Cell Death and Differentiation advance online publication, 2 June 2017; doi:10.1038/cdd.2017.89.
en
Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-κB and caspase-8-dependent apoptotic cell death.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620980/1/Lim%20et%20al.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/620980/6/Lim%20et%20al.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6209842019-08-30T11:31:23Zcom_10033_311624com_10033_6839com_10033_620626com_10033_311308com_10033_338554col_10033_621787col_10033_311625col_10033_620721col_10033_620629
Helmholtz Zentrum für Infektionsforschung Repository
author
Rahim, Muhammad Imran
author
Babbar, Anshu
author
Lienenklaus, Stefan
author
Pils, Marina
author
Rohde, M
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-06-28T13:41:37Z
2017-06-01
Degradable magnesium implant-associated infections by bacterial biofilms induce robust localized and systemic inflammatory reactions in a mouse model. 2017 Biomed Mater
1748-605X
28569671
10.1088/1748-605X/aa7667
http://hdl.handle.net/10033/620984
Biomedical materials (Bristol, England)
Biomaterial-associated Pseudomonas aeruginosa biofilm infections constitute cascade of host immune reactions ultimately leading towards implant failure. Due to lack of relevant in vivo biofilm models, majority of the studies report host immune responses against free living or planktonic bacteria while bacteria in clinical situations live more frequently as biofilm communities than as single cells. Present study investigated host immune responses against biomaterial-associated P. aeruginosa biofilms in a clinically relevant mouse model. Previously, we reported metallic magnesium, a prospective biodegradable implant, to be permissive for bacterial biofilms in vivo even though it exhibits antibacterial properties in vitro. Therefore, magnesium was employed as biomaterial to investigate in vivo biofilm formation and associated host immune responses by using two P. aeruginosa strains and two mouse strains. P. aeruginosa formed biofilms on subcutaneously implanted magnesium discs. Non-invasive in vivo imaging indicated transient inflammatory responses at control sites whereas robust prolonged interferon-β (IFN-β) expression was observed from biofilms in a transgenic animal reporter. Further, immunohistology and electron microscopic results showed that bacterial biofilms were located in two dimensions immediately on the implant surface and at a short distance in the adjacent tissue. These biofilms were surrounded by inflammatory cells (mainly polymorphonuclear cells) as compared to controls. Interestingly, even though the number of live bacteria in various organs remained below detectable levels, splenomegaly indicated systemic inflammatory processes. Overall, these findings confirmed the resistance of biofilm infections in vivo to potentially antibacterial properties of magnesium degradation products. In vivo imaging and histology indicated the induction of both, local and systemic host inflammatory responses against P. aeruginosa biofilms. Even though the innate host immune defenses could not eliminate the local infection for up to two weeks, there was no apparent systemic bacteremia and all animals investigated survived the infection.
en
Degradable magnesium implant-associated infections by bacterial biofilms induce robust localized and systemic inflammatory reactions in a mouse model.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/620984/1/Rahim%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6210242019-08-30T11:35:10Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Debarry, Jennifer
author
Heinz, D
author
Manns, M P
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-07-31T14:13:21Z
2017-07
[Individualized infection medicine : Challenges and opportunities]. 2017, 58 (7):647-649 Internist (Berl)
1432-1289
28589213
10.1007/s00108-017-0267-3
http://hdl.handle.net/10033/621024
Der Internist
[Individualized infection medicine : Challenges and opportunities].
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621024/1/Editorial_Internist_07-2017_clean.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/6210342019-08-30T11:36:32Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Kuhn, Philipp
author
Thiem, Stefanie
author
Steinert, Michael
author
Purvis, Duncan
author
Lugmayr, Veronika
author
Treutlein, Ulrich
author
Plobner, Lutz
author
Leiser, Robert-Matthias
author
Hust, Michael
author
Dübel, Stefan
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-08-02T12:02:25Z
2017-07-19
Human Anti-Lipopolysaccharid (LPS) antibodies against Legionella with high species specificity. 2017, 26 (1):29-38 Hum Antibodies
1875-869X
28582852
10.3233/HAB-170318
http://hdl.handle.net/10033/621034
Human antibodies
Legionella are Gram-negative bacteria that are ubiquitously present in natural and man-made water reservoirs. When humans inhale aerosolized water contaminated with Legionella, alveolar macrophages can be infected, which may lead to a life-threatening pneumonia called Legionnaires' disease. Due to the universal distribution of Legionella in water and their potential threat to human health, the Legionella concentration in water for human use must be strictly monitored, which is difficult since the standard detection still relies on lengthy cultivation and analysis of bacterial morphology. In this study, an antibody against L. pneumophila has been generated from the naïve human HAL antibody libraries by phage-display for the first time. The panning was performed on whole bacterial cells in order to select antibodies that bind specifically to the cell surface of untreated Legionella. The bacterial cell wall component lipopolysaccharide (LPS) was identified as the target structure. Specific binding to the important pathogenic L. pneumophila strains Corby, Philadelphia-1 and Knoxville was observed, while no binding was detected to seven members of the families Enterobacteriaceae, Pseudomonadaceae or Clostridiaceae. Production of this antibody in the recombinant scFv-Fc format using either a murine or a human Fc part allowed the set-up of a sandwich-ELISA for detection of Legionella cells. The scFv-Fc construct proved to be very stable, even when stored for several weeks at elevated temperatures. A sensitivity limit of 4,000 cells was achieved. The scFv-Fc antibody pair was integrated on a biosensor, demonstrating the specific and fast detection of L. pneumophila on a portable device. With this system, 10,000 Legionella cells were detected within 35 min. Combined with a water filtration/concentration system, this antibody may be developed into a promising reagent for rapid on-site Legionella monitoring.
en
Human Anti-Lipopolysaccharid (LPS) antibodies against Legionella with high species specificity.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621034/1/Kuhn%20et%20al.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/621034/6/Kuhn%20et%20al.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6210512019-08-30T11:34:46Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Manns, Michael P
author
Huber, Petra
author
Jaeckel, Elmar
department
Helmholtz Zentrum für Infektionsforschung GmbH, Inhoofenstr. 7, 38124 Braunschweig, Germany.
2017-08-09T12:45:51Z
2017-08-09
28427110
10.1055/s-0043-101946
http://hdl.handle.net/10033/621051
Sonderforschungsbereich SFB 738: Optimierung konventioneller und innovativer Transplantate
Article
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https://hzi.openrepository.com/bitstream/10033/621051/1/Manns%2c%20Huber%20and%20Jaeckel.pdf
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Manns, Huber and Jaeckel.pdf.txt
oai:repository.helmholtz-hzi.de:10033/6210592019-08-30T11:34:22Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Link, Alexander
author
Langner, Cosima
author
Schirrmeister, Wiebke
author
Habendorf, Wiebke
author
Weigt, Jochen
author
Venerito, Marino
author
Tammer, Ina
author
Schlüter, Dirk
author
Schlaermann, Philipp
author
Meyer, Thomas F
author
Wex, Thomas
author
Malfertheiner, Peter
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-08-17T07:58:15Z
2017-07-14
Helicobacter pylori vacA genotype is a predominant determinant of immune response to Helicobacter pylori CagA. 2017, 23 (26):4712-4723 World J. Gastroenterol.
2219-2840
28765692
10.3748/wjg.v23.i26.4712
http://hdl.handle.net/10033/621059
World journal of gastroenterology
To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response.
en
Helicobacter pylori vacA genotype is a predominant determinant of immune response to Helicobacter pylori CagA.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621059/1/Link%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6210632019-08-30T11:36:05Zcom_10033_311624com_10033_6839com_10033_620636col_10033_311625col_10033_620638
Helmholtz Zentrum für Infektionsforschung Repository
author
Swierzy, Izabela J
author
Händel, Ulrike
author
Kaever, Alexander
author
Jarek, Michael
author
Scharfe, Maren
author
Schlüter, Dirk
author
Lüder, Carsten G K
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-08-17T13:17:32Z
2017-08-03
Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions. 2017, 7 (1):7229 Sci Rep
2045-2322
28775382
10.1038/s41598-017-07838-w
http://hdl.handle.net/10033/621063
Scientific reports
The apicomplexan parasite Toxoplasma gondii infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with T. gondii. However, only a few hundred of them were regulated by infection and these largely diverged in neurons, SkMCs, astrocytes and fibroblasts indicating host cell type-specific transcriptional responses after infection. The heterogeneous transcriptomes of host cells before and during infection coincided with ~5,400 DEGs in T. gondii residing in different cell types. Finally, we identified gene clusters in both T. gondii and its host, which correlated with the predominant parasite persistence in neurons or SkMCs as compared to astrocytes or fibroblasts. Thus, heterogeneous expression profiles of different host cell types and the parasites' ability to adapting to them may govern the parasite-host cell interaction during toxoplasmosis.
en
Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621063/1/Swierzy%20et%20al.pdf
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URL
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Swierzy et al.pdf.txt
oai:repository.helmholtz-hzi.de:10033/6210682019-08-30T11:27:16Zcom_10033_311624com_10033_6839com_10033_620652col_10033_620672col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Bhushal, Sudeep
author
Wolfsmüller, Markus
author
Selvakumar, Tharini A
author
Kemper, Lucas
author
Wirth, Dagmar
author
Hornef, Mathias W
author
Hauser, Hansjörg
author
Köster, Mario
department
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-08-22T12:59:08Z
2017
Cell Polarization and Epigenetic Status Shape the Heterogeneous Response to Type III Interferons in Intestinal Epithelial Cells. 2017, 8:671 Front Immunol
1664-3224
28659914
10.3389/fimmu.2017.00671
http://hdl.handle.net/10033/621068
Frontiers in immunology
Type I and type III interferons (IFNs) are crucial components of the first-line antiviral host response. While specific receptors for both IFN types exist, intracellular signaling shares the same Jak-STAT pathway. Due to its receptor expression, IFN-λ responsiveness is restricted mainly to epithelial cells. Here, we display IFN-stimulated gene induction at the single cell level to comparatively analyze the activities of both IFN types in intestinal epithelial cells and mini-gut organoids. Initially, we noticed that the response to both types of IFNs at low concentrations is based on a single cell decision-making determining the total cell intrinsic antiviral activity. We identified histone deacetylase (HDAC) activity as a crucial restriction factor controlling the cell frequency of IFN-stimulated gene (ISG) induction upon IFN-λ but not IFN-β stimulation. Consistently, HDAC blockade confers antiviral activity to an elsewise non-responding subpopulation. Second, in contrast to the type I IFN system, polarization of intestinal epithelial cells strongly enhances their ability to respond to IFN-λ signaling and raises the kinetics of gene induction. Finally, we show that ISG induction in mini-gut organoids by low amounts of IFN is characterized by a scattered heterogeneous responsiveness of the epithelial cells and HDAC activity fine-tunes exclusively IFN-λ activity. This study provides a comprehensive description of the differential response to type I and type III IFNs and demonstrates that cell polarization in gut epithelial cells specifically increases IFN-λ activity.
en
Cell Polarization and Epigenetic Status Shape the Heterogeneous Response to Type III Interferons in Intestinal Epithelial Cells.
Article
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oai:repository.helmholtz-hzi.de:10033/6211072019-08-30T11:27:16Zcom_10033_311624com_10033_6839com_10033_311308col_10033_311625col_10033_559591
Helmholtz Zentrum für Infektionsforschung Repository
author
Dolan, Stephen K
author
Bock, Tobias
author
Hering, Vanessa
author
Owens, Rebecca A
author
Jones, Gary W
author
Blankenfeldt, Wulf
author
Doyle, Sean
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-09-13T13:49:00Z
2017-02
Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus. 2017, 7 (2) Open Biol
2046-2441
28179499
10.1098/rsob.160292
http://hdl.handle.net/10033/621107
Open biology
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S-adenosylhomocysteine (1.33 Å) and GtmA complexed to S-adenosylmethionine (2.28 Å), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of A. fumigatus to dissipate highly reactive dithiol gliotoxin, via deletion of GliT and GtmA, results in the most significant hypersensitivity to exogenous gliotoxin observed to date. Indeed, quantitative proteomic analysis of ΔgliT::ΔgtmA reveals an uncontrolled over-activation of the gli-cluster upon gliotoxin exposure. The data presented herein reveal, for the first time, the extreme risk associated with intracellular dithiol gliotoxin biosynthesis-in the absence of an efficient dismutation capacity. Significantly, a previously concealed protective role for GtmA and functionality of ETP bis-thiomethylation as an ancestral protection strategy against dithiol compounds is now evident.
en
Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621107/1/Dolan%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6211202019-08-30T11:34:22Zcom_10033_311624com_10033_6839com_10033_620652col_10033_620672col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Cebula, Marcin
author
Riehn, Mathias
author
Hillebrand, Upneet
author
Kratzer, Ramona F
author
Kreppel, Florian
author
Koutsoumpli, Georgia
author
Daemen, Toos
author
Hauser, Hansjoerg
author
Wirth, Dagmar
department
Helmholtz -Zentrum für Infektionsforschung GmbH. Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-09-25T14:24:23Z
2017-07-14
TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall. 2017 Mol. Ther.
1525-0024
28716576
10.1016/j.ymthe.2017.06.018
http://hdl.handle.net/10033/621120
Molecular therapy : the journal of the American Society of Gene Therapy
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination-induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response.
en
TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621120/1/Cebula%20et%20al.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/621120/2/Cebula_Suppl.pdf
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URL
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URL
https://hzi.openrepository.com/bitstream/10033/621120/9/Cebula_Suppl.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6211282019-08-30T11:34:48Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Nonnenmacher, Yannic
author
Palorini, Roberta
author
d'Herouël, Aymeric Fouquier
author
Krämer, Lisa
author
Neumann-Schaal, Meina
author
Chiaradonna, Ferdinando
author
Skupin, Alexander
author
Wegner, Andre
author
Hiller, Karsten
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-10-06T09:18:42Z
2017-09
Analysis of mitochondrial metabolism in situ: Combining stable isotope labeling with selective permeabilization. 2017, 43 (Pt B):147-155 Metab. Eng.
1096-7184
27988388
10.1016/j.ymben.2016.12.005
http://hdl.handle.net/10033/621128
Metabolic engineering
To date, it is well-established that mitochondrial dysfunction does not only play a vital role in cancer but also in other pathological conditions such as neurodegenerative diseases and inflammation. An important tool for the analysis of cellular metabolism is the application of stable isotope labeled substrates, which allow for the tracing of atoms throughout metabolic networks. While such analyses yield very detailed information about intracellular fluxes, the determination of compartment specific fluxes is far more challenging. Most approaches for the deconvolution of compartmented metabolism use computational models whereas experimental methods are rare. Here, we developed an experimental setup based on selective permeabilization of the cytosolic membrane that allows for the administration of stable isotope labeled substrates directly to mitochondria. We demonstrate how this approach can be used to infer metabolic changes in mitochondria induced by either chemical or genetic perturbations and give an outlook on its potential applications.
en
Analysis of mitochondrial metabolism in situ: Combining stable isotope labeling with selective permeabilization.
Article
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oai:repository.helmholtz-hzi.de:10033/6211302019-08-30T11:28:51Zcom_10033_311624com_10033_6839com_10033_620652col_10033_620672col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Gödecke, Natascha
author
Zha, Lisha
author
Spencer, Shawal
author
Behme, Sara
author
Riemer, Pamela
author
Rehli, Michael
author
Hauser, Hansjörg
author
Wirth, Dagmar
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, D38124 Braunschweig, Germany.
2017-10-09T13:56:28Z
2017-09-19
Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation. 2017, 45 (16):e147 Nucleic Acids Res.
1362-4962
28934472
10.1093/nar/gkx601
http://hdl.handle.net/10033/621130
Nucleic acids research
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood. To reactivate Tet cassettes a synthetic fusion protein was constructed and expressed in silenced cells. This protein includes the enzymatic domains of ten eleven translocation methylcytosine dioxygenase 1 (TET-1) as well as the Tet repressor DNA binding domain. Expression of the synthetic fusion protein and Doxycycline treatment allowed targeted demethylation of the Tet promoter in the ROSA26 locus and in another genomic site, rescuing transgene expression in cells and transgenic mice. Thus, inducible, reversible and site-specific epigenetic modulation is a promising strategy for reactivation of silenced transgene expression, independent of the integration site.
en
Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/6211362019-08-30T11:27:16Zcom_10033_311624com_10033_6839com_10033_620618col_10033_311625col_10033_620619
Helmholtz Zentrum für Infektionsforschung Repository
author
Rox, Katharina
author
Jansen, Rolf
author
Loof, Torsten G.
author
Gillen, Christine M.
author
Bernecker, Steffen
author
Walker, Mark J.
author
Chhatwal, Gursharan Singh
author
Müller, Rolf
department
Helmholtz-Institut für pharmazeutische Forschung Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-10-12T09:13:35Z
2017-09-18
Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection 2017, 7 (1) Scientific Reports
2045-2322
10.1038/s41598-017-11276-z
http://hdl.handle.net/10033/621136
Scientific Reports
In contrast to mild infections of Group A Streptococcus (GAS) invasive infections of GAS still pose a serious health hazard: GAS disseminates from sterile sites into the blood stream or deep tissues and causes sepsis or necrotizing fasciitis. In this case antibiotics do not provide an effective cure as the bacteria are capable to hide from them very quickly. Therefore, new remedies are urgently needed. Starting from a myxobacterial natural products screening campaign, we identified two fatty acids isolated from myxobacteria, linoleic and palmitoleic acid, specifically blocking streptokinase-mediated activation of plasminogen and thereby preventing streptococci from hijacking the host’s plasminogen/plasmin system. This activity is not inherited by other fatty acids such as oleic acid and is not attributable to the killing of streptococci. Moreover, both fatty acids are superior in their inhibitory properties compared to two clinically used drugs (tranexamic or ε-amino caproic acid) as they show 500–1000 fold lower IC50 values. Using a humanized plasminogen mouse model mimicking the clinical situation of a local GAS infection that becomes systemic, we demonstrate that these fatty acids ameliorate invasive GAS infection significantly. Consequently, linoleic and palmitoleic acid are possible new options to combat GAS invasive diseases.
Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621136/1/Rox%20et%20al.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/6211622019-08-30T11:28:51Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Debarry, Jennifer
author
Cornberg, Markus
author
Manns, Michael P
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-11-06T14:40:59Z
2017-01
Challenges in warranting access to prophylaxis and therapy for hepatitis B virus infection. 2017, 37 Suppl 1:67-72 Liver Int.
1478-3231
28052625
10.1111/liv.13320
http://hdl.handle.net/10033/621162
Liver international : official journal of the International Association for the Study of the Liver
Despite an available vaccine and efficient treatment for hepatitis B virus (HBV) infection, chronic HBV infection still remains a major global threat, and one of the top 20 causes of human mortality worldwide. One of the major challenges in controlling HBV infection is the high number of undiagnosed chronic carriers and the lack of access to prophylaxis and treatment in several parts of the world. We discuss relevant barriers that need to be overcome to achieve global control of HBV infection and make eradication possible. Most important, vaccination must be scaled-up to lower the risk of vertical transmission and decrease the number of new infections, and comprehensive screening programs must be linked to care to obtain a better rate of diagnosis and treatment. This can probably only be achieved if sustainable funding is available. We therefore emphasize the importance of making the management of viral hepatitis a global health priority.
en
Challenges in warranting access to prophylaxis and therapy for hepatitis B virus infection.
Article
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oai:repository.helmholtz-hzi.de:10033/6211682019-08-30T11:34:43Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Manns, Michael P
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-11-07T15:19:40Z
2017-10
Hepatitis D virus in Africa: several unmet needs. 2017, 5 (10):e953-e954 Lancet Glob Health
2214-109X
28911754
10.1016/S2214-109X(17)30345-5
http://hdl.handle.net/10033/621168
The Lancet. Global health
en
Hepatitis D virus in Africa: several unmet needs.
Article
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oai:repository.helmholtz-hzi.de:10033/6212192019-08-30T11:35:36Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Nishanth, G
author
Wolleschak, D
author
Fahldieck, C
author
Fischer, T
author
Mullally, A
author
Perner, F
author
Schnöder, T M
author
Just, S
author
Heidel, F H
author
Schlüter, D
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
2018-01-02T14:52:32Z
2017-04
Gain of function in Jak2V617F-positive T-cells. 2017, 31 (4):1000-1003 Leukemia
1476-5551
28074070
10.1038/leu.2017.6
http://hdl.handle.net/10033/621219
Leukemia
en
Gain of function in Jak2V617F-positive T-cells.
Article
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oai:repository.helmholtz-hzi.de:10033/6212372019-08-30T11:35:10Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Manns, Michael P
department
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany.
2018-01-17T15:24:00Z
2016-12
Future Organization of Clinical Research in Germany: The Road to the "German Centre for Digestive Health" (GCDH). 2016, 54 (12):1293-1295 Z Gastroenterol
1439-7803
27936478
10.1055/s-0042-118288
http://hdl.handle.net/10033/621237
Zeitschrift fur Gastroenterologie
en
Future Organization of Clinical Research in Germany: The Road to the "German Centre for Digestive Health" (GCDH).
Other
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Manns.pdf.txt
oai:repository.helmholtz-hzi.de:10033/6212382019-08-30T11:35:10Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Manns, Michael P
author
Jaeckel, Elmar
author
Taubert, Richard
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
2018-01-18T09:28:42Z
2017-11-08
Budesonide in Autoimmune Hepatitis: The Right Drug at the Right Time for the Right Patient. 2017 Clin. Gastroenterol. Hepatol.
1542-7714
29128475
10.1016/j.cgh.2017.11.003
http://hdl.handle.net/10033/621238
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
en
Budesonide in Autoimmune Hepatitis: The Right Drug at the Right Time for the Right Patient.
Article
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oai:repository.helmholtz-hzi.de:10033/6213362020-06-30T13:26:39Zcom_10033_196529com_10033_56876com_10033_6839col_10033_196534col_10033_621495
Helmholtz Zentrum für Infektionsforschung Repository
author
Junge, Norman
author
Yuan, Qinggong
author
Vu, Thu Huong
author
Krooss, Simon
author
Bednarski, Christien
author
Balakrishnan, Asha
author
Cathomen, Toni
author
Manns, Michael P
author
Baumann, Ulrich
author
Sharma, Amar Deep
author
Ott, Michael
department
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-04-05T11:55:04Z
2018-02-27
Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model. 2018, 10 (2):277-286 World J Hepatol
1948-5182
29527263
10.4254/wjh.v10.i2.277
http://hdl.handle.net/10033/621336
World journal of hepatology
To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout (Fah-/-)mice by homologous-recombination-mediated targeted addition of theFahgene.
en
Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model.
Article
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oai:repository.helmholtz-hzi.de:10033/6213602019-08-30T11:33:57Zcom_10033_620533com_10033_311624com_10033_6839com_10033_338554col_10033_621787col_10033_620534col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Rahim, Muhammad Imran
author
Weizbauer, Andreas
author
Evertz, Florian
author
Hoffmann, Andrea
author
Rohde, M
author
Glasmacher, Birgit
author
Windhagen, Henning
author
Gross, Gerhard
author
Seitz, Jan-Marten
author
Mueller, Peter P
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-04-24T09:06:49Z
2017
Differential magnesium implant corrosion coat formation and contribution to bone bonding. 2017, 105 (3):697-709 J Biomed Mater Res A
1552-4965
27770566
10.1002/jbm.a.35943
http://hdl.handle.net/10033/621360
Journal of biomedical materials research. Part A
Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels. Similarly, in soft tissue no bone induction by metallic magnesium or by the corrosion product magnesium hydroxide could be observed in a mouse model. Motivated by the comparatively rapid accumulation solid corrosion products physicochemical processes were examined as an alternative mechanism to explain the stimulation of bone growth by magnesium-based implants. During exposure to physiological solutions a structured corrosion coat formed on magnesium whereby the elements calcium and phosphate were enriched in the outermost layer which could play a role in the established biocompatible behavior of magnesium implants. When magnesium pins were inserted into avital bones, corrosion lead to increases in the pull out force, suggesting that the expanding corrosion layer was interlocking with the surrounding bone. Since mechanical stress is a well-established inducer of bone growth, volume increases caused by the rapid accumulation of corrosion products and the resulting force development could be a key mechanism and provide an explanation for the observed stimulatory effects of magnesium-based implants in hard tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 697-709, 2017.
en
Differential magnesium implant corrosion coat formation and contribution to bone bonding.
Article
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oai:repository.helmholtz-hzi.de:10033/6214092019-08-30T11:32:37Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Strunz, Benedikt
author
Hengst, Julia
author
Deterding, Katja
author
Manns, Michael P
author
Cornberg, Markus
author
Ljunggren, Hans-Gustaf
author
Wedemeyer, Heiner
author
Björkström, Niklas K
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-06-25T13:16:54Z
2018-06-11
2041-1723
29891939
10.1038/s41467-018-04685-9
http://hdl.handle.net/10033/621409
Diversity is a central requirement for the immune system's capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
Attribution-NonCommercial-ShareAlike 3.0 United States
Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/6214222019-08-30T11:33:27Zcom_10033_311624com_10033_6839com_10033_620636col_10033_311625col_10033_620638
Helmholtz Zentrum für Infektionsforschung Repository
author
Kremling, Andreas
author
Goehler, Anna
author
Jahreis, Knut
author
Nees, Markus
author
Auerbach, Benedikt
author
Schmidt-Heck, Wolfgang
author
Kökpinar, Oznur
author
Geffers, Robert
author
Rinas, Ursula
author
Bettenbrock, Katja
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-07-05T14:17:15Z
2012-11-12
2218-1989
24957765
10.3390/metabo2040844
http://hdl.handle.net/10033/621422
Metabolism and signalling are tightly coupled in bacteria. Combining several theoretical approaches, a core model is presented that describes transcriptional and allosteric control of glycolysis in Escherichia coli. Experimental data based on microarrays, signalling components and extracellular metabolites are used to estimate kinetic parameters. A newly designed strain was used that adjusts the incoming glucose flux into the system and allows a kinetic analysis. Based on the results, prediction for intracelluar metabolite concentrations over a broad range of the growth rate could be performed and compared with data from literature.
Attribution-NonCommercial-ShareAlike 3.0 United States
Analysis and Design of Stimulus Response Curves of E. coli.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621422/1/Kremling%20et%20al.pdf
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URL
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Kremling et al.pdf.txt
oai:repository.helmholtz-hzi.de:10033/6214272018-07-19T17:28:27Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Strunz, Benedikt
author
Hengst, Julia
author
Deterding, Katja
author
Manns, Michael P
author
Cornberg, Markus
author
Ljunggren, Hans-Gustaf
author
Wedemeyer, Heiner
author
Björkström, Niklas K
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-07-19T12:06:33Z
2018-06-11
2041-1723
29891939
10.1038/s41467-018-04685-9
http://hdl.handle.net/10033/621427
Diversity is a central requirement for the immune system's capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
Attribution-NonCommercial-ShareAlike 3.0 United States
Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621427/1/Meyer%20et%20al.pdf
File
MD5
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URL
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File
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Meyer et al.pdf.txt
oai:repository.helmholtz-hzi.de:10033/6214392019-08-30T11:34:45Zcom_10033_311624com_10033_6839com_10033_620601com_10033_620652col_10033_620672col_10033_311625col_10033_620602
Helmholtz Zentrum für Infektionsforschung Repository
author
Selvakumar, Tharini A
author
Bhushal, Sudeep
author
Kalinke, Ulrich
author
Wirth, Dagmar
author
Hauser, Hansjörg
author
Köster, Mario
author
Hornef, Mathias W
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-08-07T11:47:28Z
2017-01-01
1664-3224
29085367
10.3389/fimmu.2017.01302
http://hdl.handle.net/10033/621439
Type I (α and β) and type III (λ) interferons (IFNs) induce the expression of a large set of antiviral effector molecules
en
Attribution-NonCommercial-ShareAlike 3.0 United States
gastrointestinal tract
interferon-lambda
interleukin 28 receptor
intestinal epithelium
transcription
Identification of a Predominantly Interferon-λ-Induced Transcriptional Profile in Murine Intestinal Epithelial Cells.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621439/1/Selvakumar%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6214402019-08-30T11:35:10Zcom_10033_311624com_10033_6839com_10033_311308col_10033_311625col_10033_620721
Helmholtz Zentrum für Infektionsforschung Repository
author
Quaas, Bastian
author
Burmeister, Laura
author
Li, Zhaopeng
author
NIMTZ, MANFRED
author
Hoffmann, Andrea
author
Rinas, Ursula
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-08-07T12:49:29Z
13595113
10.1016/j.procbio.2018.02.001
http://hdl.handle.net/10033/621440
en
Attribution-NonCommercial-ShareAlike 3.0 United States
Properties of dimeric, disulfide-linked rhBMP-2 recovered from E. coli derived inclusion bodies by mild extraction or chaotropic solubilization and subsequent refolding
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621440/1/Quaas%20et%20al.pdf
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https://hzi.openrepository.com/bitstream/10033/621440/2/supplementary%20material%20zu%20Quaas%20et%20al.pdf
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URL
https://hzi.openrepository.com/bitstream/10033/621440/5/Quaas%20et%20al.pdf.txt
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URL
https://hzi.openrepository.com/bitstream/10033/621440/7/supplementary%20material%20zu%20Quaas%20et%20al.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6214872019-08-30T11:27:45Zcom_10033_311624com_10033_6839com_10033_311308col_10033_311625col_10033_620721
Helmholtz Zentrum für Infektionsforschung Repository
author
Roth, Gustavo
author
Vanz, Ana Letícia
author
Lünsdorf, Heinrich
author
Nimtz, Manfred
author
Rinas, Ursula
department
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-09-18T13:36:58Z
2018-08-09
1475-2859
30092809
10.1186/s12934-018-0970-3
http://hdl.handle.net/10033/621487
Secretory recombinant protein production with Pichia (syn. Komagataella) pastoris is commonly associated with the induction of an unfolded protein response (UPR) usually apparent through increased intracellular levels of endoplasmic reticulum (ER) resident chaperones such as Kar2/Bip. During methanol-induced secretory production of an insulin precursor (IP) under industrially relevant fed-batch conditions the initially high level of intracellular Kar2/Bip after batch growth on glycerol unexpectedly declined in the following methanol fed-batch phase misleadingly suggesting that IP production had a low impact on UPR activation. Analysis of the protein production independent level of Kar2/Bip revealed that high Kar2/Bip levels were reached in the exponential growth phase of glycerol batch cultures followed by a strong decline of Kar2/Bip during entry into stationary phase. Ultra-structural cell morphology studies revealed autophagic processes (e.g. ER phagy) at the end of the glycerol batch phase most likely responsible for the degradation of ER resident chaperones such as Kar2/Bip. The pre-induction level of Kar2/Bip did not affect the IP secretion efficiency in the subsequent methanol-induced IP production phase. During growth on methanol intracellular Kar2/Bip levels declined in IP producing and non-producing host cells. However, extracellular accumulation of Kar2/Bip was observed in IP-producing cultures but not in non-producing controls. Most importantly, the majority of the extracellular Kar2/Bip accumulated in the culture supernatant of IP producing cells as truncated protein (approx. 35 kDa). Rapid growth leads to higher basal levels of the major UPR marker protein Kar2/Bip independent of recombinant protein production. Entry into stationary phase or slower growth on poorer substrate, e.g. methanol, leads to a lower basal Kar2/Bip level. Methanol-induced secretory IP production elicits a strong UPR activation which counteracts the reduced UPR during slow growth on methanol. The major ER chaperone Kar2/Bip is found together with recombinant IP in the culture medium where full-length Kar2/Bip accumulates in addition to large amounts of truncated Kar2/Bip. Thus, for judging UPR activating properties of the produced protein it is important to additionally analyze the medium not only for intact Kar2/Bip but also for truncated versions of this UPR reporter protein.
Attribution-NonCommercial-ShareAlike 3.0 United States
Autophagy
Kar2/Bip
Pichia pastoris
Unfolded protein response
Fate of the UPR marker protein Kar2/Bip and autophagic processes in fed-batch cultures of secretory insulin precursor producing Pichia pastoris.
Article
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
URL
https://hzi.openrepository.com/bitstream/10033/621487/1/Roth%20et%20al.pdf
File
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URL
https://hzi.openrepository.com/bitstream/10033/621487/4/Roth%20et%20al.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6214962019-08-30T11:30:31Zcom_10033_6839col_10033_621495
Helmholtz Zentrum für Infektionsforschung Repository
author
Velasquez, Lis Noelia
author
Stüve, Philipp
author
Gentilini, Maria Virginia
author
Swallow, Maxine
author
Bartel, Judith
author
Lycke, Nils Yngve
author
Barkan, Daniel
author
Martina, Mariana
author
Lujan, Hugo D
author
Kalay, Hakan
author
van Kooyk, Yvette
author
Sparwasser, Tim D
author
Berod, Luciana
department
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-09-25T13:27:07Z
2018-01-01
1664-3224
29662482
10.3389/fimmu.2018.00471
http://hdl.handle.net/10033/621496
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells
(DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags
are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors.
Here, we explored DC-specifc-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as
a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse
model that expresses human DC-SIGN under the control of the murine CD11c promoter.
We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to
Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall
component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces
strong Ag-specifc CD4+ T-cell responses. Improved anti-mycobacterial immunity was
accompanied by increased frequencies of Ag-specifc IFN-γ+ IL-2+ TNF-α+ polyfunctional
CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study
we provide the proof of concept that the human DC-SIGN receptor can be effciently
exploited for vaccine purposes to promote immunity against mycobacterial infections.
Attribution-NonCommercial-ShareAlike 3.0 United States
Ag85B
DC-specific-ICAM3-grabbing-nonintegrin
dendritic cells
tuberculosis
vaccine
Targeting Antigens to Dendritic Cells the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621496/1/Velasquez%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6215172019-08-30T11:29:46Zcom_10033_6839col_10033_621495
Helmholtz Zentrum für Infektionsforschung Repository
author
Abeln, Markus
author
Borst, Kristina M
author
Cajic, Samanta
author
Thiesler, Hauke
author
Kats, Elina
author
Albers, Iris
author
Kuhn, Maike
author
Kaever, Volkhard
author
Rapp, Erdmann
author
Münster-Kühnel, Anja
author
Weinhold, Birgit
department
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-10-12T08:16:40Z
2017-07-04
1439-7633
28374933
10.1002/cbic.201700083
http://hdl.handle.net/10033/621517
The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. In order to elucidate the impact of sialylation on differentiation processes in the absence of maternal influences, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the ability to activate Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues, as well as intracellular accumulation of free Sia. Remarkably, these changes did not impact intracellular metabolites or the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas
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CMP-sialic acid synthase
differentiation
glycosylation
metabolism
sialic acids
Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro.
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621517/1/Abeln%20%20et%20al.pdf
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URL
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oai:repository.helmholtz-hzi.de:10033/6215192019-08-30T11:29:45Zcom_10033_311624com_10033_6839com_10033_620636col_10033_311625col_10033_620637
Helmholtz Zentrum für Infektionsforschung Repository
author
Müsken, Mathias
author
Pawar, Vinay
author
Schwebs, Timo
author
Bähre, Heike
author
Felgner, Sebastian
author
Weiss, Siegfried
author
Häussler, Susanne
department
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2018-10-19T13:48:16Z
2018-10-08
1098-6596
30297365
10.1128/AAC.01635-18
http://hdl.handle.net/10033/621519
Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse
physico-chemical insults. In addition to the general recalcitrance of biofilm-bacteria, high
bacterial loads in biofilm-associated infections significantly diminishes the efficacy of
antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial
treatment protocols, that have been established to serve the eradication of acute infections, fail
to clear biofilm-associated chronic infections. In the present study, we applied automated
confocal microscopy on Pseudomonas aeruginosa to monitor dynamic killing of biofilm-grown
bacteria by tobramycin and colistin in real-time. We revealed that the time required for
surviving bacteria to repopulate the biofilm could be taken as measure for effectiveness of the
antimicrobial treatment. It depends on the: i) nature and concentration of the antibiotic, ii)
duration of antibiotic treatment; iii) application as mono or combination therapy and iv) time
intervals of drug administration. The vicious cycle of killing and repopulation of biofilm
bacteria could also be broken in an in vivo model system by applying successive antibiotic
dosages with time intervals that do not allow full reconstitution of the biofilm communities.
Treatment regimens that consider the important aspects of antimicrobial killing kinetics bear
the potential to improve control of biofilm regrowth. This is an important and underestimated
factor that is bound to ensure sustainable treatment success of chronic infections.
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Breaking the vicious cycle of antibiotic killing and regrowth of biofilm-residing .
Article
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URL
https://hzi.openrepository.com/bitstream/10033/621519/1/M%c3%bcsken%20et%20al.pdf
File
MD5
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Müsken et al.pdf
URL
https://hzi.openrepository.com/bitstream/10033/621519/4/M%c3%bcsken%20et%20al.pdf.txt
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oai:repository.helmholtz-hzi.de:10033/6215452019-08-30T11:30:26Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Meiser, Johannes
author
Kraemer, Lisa
author
Jaeger, Christian
author
Madry, Henning
author
Link, Andreas
author
Lepper, Philipp M
author
Hiller, Karsten
author
Schneider, Jochen G
department
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2018-11-08T13:10:12Z
2018-08-14
1949-2553
30181801
10.18632/oncotarget.25956
http://hdl.handle.net/10033/621545
Itaconic acid is produced by mammalian leukocytes upon pro-inflammatory activation. It appears to inhibit bacterial growth and to rewire the metabolism of the host cell by inhibiting succinate dehydrogenase. Yet, it is unknown whether itaconic acid acts only intracellularly, locally in a paracrine fashion, or whether it is even secreted from the inflammatory cells at meaningful levels in peripheral blood of patients with severe inflammation or sepsis. The aim of this study was to determine the release rate of itaconic acid from pro-inflammatory activated macrophages
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Immunology
biomarker
inflammation
itaconic acid
metabolism
sepsis
Itaconic acid indicates cellular but not systemic immune system activation.
Article
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oai:repository.helmholtz-hzi.de:10033/6215672019-08-30T11:29:43Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Broglia, Laura
author
Materne, Solange
author
Lécrivain, Anne-Laure
author
Hahnke, Karin
author
Le Rhun, Anaïs
author
Charpentier, Emmanuelle
department
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2018-11-15T12:46:50Z
2018-01-01
1555-8584
30290721
10.1080/15476286.2018.1532253
http://hdl.handle.net/10033/621567
Endoribonuclease Y (RNase Y) is a crucial regulator of virulence in Gram-positive bacteria. In the human pathogen Streptococcus pyogenes, RNase Y is required for the expression of the major secreted virulence factor streptococcal pyrogenic exotoxin B (SpeB), but the mechanism involved in this regulation remains elusive. Here, we demonstrate that the 5' untranslated region of speB mRNA is processed by several RNases including RNase Y. In particular, we identify two RNase Y cleavage sites located downstream of a guanosine (G) residue. To assess whether this nucleotide is required for RNase Y activity in vivo, we mutated it and demonstrate that the presence of this G residue is essential for the processing of the speB mRNA 5' UTR by RNase Y. Although RNase Y directly targets and processes speB, we show that RNase Y-mediated regulation of speB expression occurs primarily at the transcriptional level and independently of the processing in the speB mRNA 5' UTR. To conclude, we demonstrate for the first time that RNase Y processing of an mRNA target requires the presence of a G. We also provide new insights on the speB 5' UTR and on the role of RNase Y in speB regulation.
Attribution-NonCommercial-ShareAlike 3.0 United States
5′ untranslated region
RNase Y
Streptococcus pyogenes
speB
transcriptional regulation
virulence
RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B.
Article
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URL
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oai:repository.helmholtz-hzi.de:10033/6215702019-08-30T11:29:43Zcom_10033_311624com_10033_6839col_10033_311625
Helmholtz Zentrum für Infektionsforschung Repository
author
Jupa, K.L.
author
Manns, M.P.
author
Jäckel, E
department
DZIF,Deutsches Zentrum für Infektionsforschung; HZI, Helmholtz-Zentrum für Infektiondforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig.
2018-11-16T09:54:24Z
0494464X
http://hdl.handle.net/10033/621570
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Attribution-NonCommercial-ShareAlike 3.0 United States
Die nicht-alkoholische Fettlebererkrankung : Die Rolle der Leber im metabolischen Syndrom
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