2024-03-28T19:45:01Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/1399622019-08-30T11:33:57Zcom_10033_620533col_10033_620538
Lu, Xin
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500
Sun, Jibin
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Nimtz, Manfred
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500
Wissing, Josef
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Zeng, An-Ping
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Rinas, Ursula
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Helmholtz Center for Infection Research, Inhoffenstr, Braunschweig, Germany.
2011-08-17T13:57:00Z
2011-08-17T13:57:00Z
2010
The intra- and extracellular proteome of Aspergillus niger growing on defined medium with xylose or maltose as carbon substrate. 2010, 9:23 Microb. Cell Fact.
1475-2859
20406453
10.1186/1475-2859-9-23
http://hdl.handle.net/10033/139962
Microbial cell factories
The filamentous fungus Aspergillus niger is well-known as a producer of primary metabolites and extracellular proteins. For example, glucoamylase is the most efficiently secreted protein of Aspergillus niger, thus the homologous glucoamylase (glaA) promoter as well as the glaA signal sequence are widely used for heterologous protein production. Xylose is known to strongly repress glaA expression while maltose is a potent inducer of glaA promoter controlled genes. For a more profound understanding of A. niger physiology, a comprehensive analysis of the intra- and extracellular proteome of Aspergillus niger AB1.13 growing on defined medium with xylose or maltose as carbon substrate was carried out using 2-D gel electrophoresis/Maldi-ToF and nano-HPLC MS/MS.
en
Air
Aspergillus niger
Bioreactors
Carbon
Fungal Proteins
Hydrogen-Ion Concentration
Maltose
Proteome
Proteomics
Xylose
The intra- and extracellular proteome of Aspergillus niger growing on defined medium with xylose or maltose as carbon substrate.
Article
2018-06-13T04:24:35Z
The filamentous fungus Aspergillus niger is well-known as a producer of primary metabolites and extracellular proteins. For example, glucoamylase is the most efficiently secreted protein of Aspergillus niger, thus the homologous glucoamylase (glaA) promoter as well as the glaA signal sequence are widely used for heterologous protein production. Xylose is known to strongly repress glaA expression while maltose is a potent inducer of glaA promoter controlled genes. For a more profound understanding of A. niger physiology, a comprehensive analysis of the intra- and extracellular proteome of Aspergillus niger AB1.13 growing on defined medium with xylose or maltose as carbon substrate was carried out using 2-D gel electrophoresis/Maldi-ToF and nano-HPLC MS/MS.
ORIGINAL
Lu et al_final.pdf
Lu et al_final.pdf
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LICENSE
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TEXT
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Lu et al_final.pdf.txt
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10033/139962
oai:hzi.openrepository.com:10033/139962
2019-08-30 11:33:57.231
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/1903392019-08-30T11:33:28Zcom_10033_620533col_10033_620538
Koutinas, Michalis
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Kiparissides, Alexandros
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Lam, Ming-Chi
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Silva-Rocha, Rafael
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Godinho, Miguel
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de Lorenzo, Victor
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Martins dos Santos, Vitor A.P.
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500
Pistikopoulos, Efstratios N.
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500
Mantalaris, Athanasios
a4c3c2564c9e1a34ed01e24650b49671
500
Helmholtz Center for Infection Research (HZI), 38124 Braunschweig, Germany.
2011-11-22T15:39:44Z
2011-11-22T15:39:44Z
2011-11-22T15:39:44Z
Improving the prediction of Pseudomonas putida mt-2 growth kinetics with the use of a gene expression regulation model of the TOL plasmid 2011, 55 (2):108 Biochemical Engineering Journal
1369703X
10.1016/j.bej.2011.03.012
http://hdl.handle.net/10033/190339
Biochemical Engineering Journal
null
http://linkinghub.elsevier.com/retrieve/pii/S1369703X11000829
Improving the prediction of Pseudomonas putida mt-2 growth kinetics with the use of a gene expression regulation model of the TOL plasmid
Article
2018-05-23T10:17:02Z
ORIGINAL
Koutinas et al_final.pdf
Koutinas et al_final.pdf
original manuscript
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table 5
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LICENSE
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THUMBNAIL
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TEXT
Koutinas et al_final.pdf.txt
Koutinas et al_final.pdf.txt
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oai:hzi.openrepository.com:10033/190339
2019-08-30 11:33:28.75
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2162972019-08-30T11:33:57Zcom_10033_620533col_10033_620538
Hassan, Rabeay Y A
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Bilitewski, Ursula
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Biological Systems Analysis Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
2012-03-22T14:02:04Z
2012-03-22T14:02:04Z
2011-12-01
A viability assay for Candida albicans based on the electron transfer mediator 2,6-dichlorophenolindophenol. 2011, 419 (1):26-32 Anal. Biochem.
1096-0309
21864496
10.1016/j.ab.2011.07.025
http://hdl.handle.net/10033/216297
Analytical biochemistry
Candida albicans is an opportunistic fungal pathogen with comparably high respiratory activity. Thus, we established a viability test based on 2,6-dichlorophenolindophenol (DCIP), a membrane-permeable electron transfer agent. NADH dehydrogenases catalyze the reduction of DCIP by NADH, and the enzymatic activity can be determined either electrochemically via oxidation reactions of DCIP or photometrically. Among the specific respiratory chain inhibitors, only the complex I inhibitor rotenone decreased the DCIP signal from C. albicans, leaving residual activity of approximately 30%. Thus, the DCIP-reducing activity of C. albicans was largely dependent on complex I activity. C. albicans is closely related to the complex I-negative yeast Saccharomyces cerevisiae, which had previously been used in DCIP viability assays. Via comparative studies, in which we included the pathogenic complex I-negative yeast Candida glabrata, we could define assay conditions that allow a distinction of complex I-negative and -positive organisms. Basal levels of DCIP turnover by S.cerevisiae and C. glabrata were only 30% of those obtained from C. albicans but could be increased to the C. albicans level by adding glucose. No significant increases were observed with galactose. DCIP reduction rates from C. albicans were not further increased by any carbon source.
en
Archived with thanks to Analytical biochemistry
2,6-Dichloroindophenol
Candida albicans
Candida glabrata
Catalysis
Color
Electrochemistry
Electron Transport
Enzyme Activation
Fungal Proteins
Galactose
Glucose
Microbial Viability
Microbiological Techniques
NAD
NADH Dehydrogenase
Oxidation-Reduction
Oxygen
Rotenone
Saccharomyces cerevisiae
Spectrophotometry
A viability assay for Candida albicans based on the electron transfer mediator 2,6-dichlorophenolindophenol.
Article
2018-06-13T01:19:55Z
Candida albicans is an opportunistic fungal pathogen with comparably high respiratory activity. Thus, we established a viability test based on 2,6-dichlorophenolindophenol (DCIP), a membrane-permeable electron transfer agent. NADH dehydrogenases catalyze the reduction of DCIP by NADH, and the enzymatic activity can be determined either electrochemically via oxidation reactions of DCIP or photometrically. Among the specific respiratory chain inhibitors, only the complex I inhibitor rotenone decreased the DCIP signal from C. albicans, leaving residual activity of approximately 30%. Thus, the DCIP-reducing activity of C. albicans was largely dependent on complex I activity. C. albicans is closely related to the complex I-negative yeast Saccharomyces cerevisiae, which had previously been used in DCIP viability assays. Via comparative studies, in which we included the pathogenic complex I-negative yeast Candida glabrata, we could define assay conditions that allow a distinction of complex I-negative and -positive organisms. Basal levels of DCIP turnover by S.cerevisiae and C. glabrata were only 30% of those obtained from C. albicans but could be increased to the C. albicans level by adding glucose. No significant increases were observed with galactose. DCIP reduction rates from C. albicans were not further increased by any carbon source.
ORIGINAL
Hassan_Bilitewski_final.pdf
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2019-08-30 11:33:57.31
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2697162019-08-30T11:32:41Zcom_10033_620533col_10033_620538
Buschart, Anna
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500
Burakowska, Anna
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500
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Biological Systems Analysis, Helmholtz Centre for Infection Research, Braunschweig, Germany.
2013-02-18T15:19:02Z
2013-02-18T15:19:02Z
2012-12
The fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans. 2012, 61 (Pt 12):1696-703 J. Med. Microbiol.
1473-5644
22918865
10.1099/jmm.0.050963-0
http://hdl.handle.net/10033/269716
Journal of medical microbiology
The fungicide fludioxonil is widely used in agriculture. Residua of this fungicide are occasionally detected in fruits and can therefore be ingested by humans. The human fungal pathogen Candida albicans expresses the target of fludioxonil, Nik1p, a type III histidine kinase involved in stress response. Inhibition of yeast and hyphae growth was hardly observable after treatment of C. albicans SC5314 with fludioxonil. As a side effect, however, we observed a concentration-dependent induction of the expression of the genes CDR1 and CDR2, encoding ATP-binding cassette (ABC) transporters. This was independent of the presence of the target of fludioxonil as induction was also observed in a Δnik1 deletion mutant. Deletion of the CDR1 gene aggravated the inhibition of germ tube formation by fludioxonil, indicating that, in the wild-type, the fungicide was discharged from the cell by Cdr1p. Cdr1p is also known as a resistance factor of C. albicans against the commonly used antimycotic fluconazole. Thus, the effect of concurrent exposure to fludioxonil and known cargoes of ABC transporters on their extrusion and the growth of C. albicans was examined. Pre-incubation with fludioxonil decreased the export rate of rhodamine 6G. The resistance to fluconazole was increased by fludioxonil, independently of Nik1p. Therefore, exposure of C. albicans to fludioxonil may lead to increased resistance to fluconazole treatment.
en
Archived with thanks to Journal of medical microbiology
ATP-Binding Cassette Transporters
Antifungal Agents
Candida albicans
Candidiasis
Cell Proliferation
Dioxoles
Drug Resistance, Fungal
Fluconazole
Fungal Proteins
Fungicides, Industrial
Gene Expression Regulation, Fungal
Humans
Membrane Transport Proteins
Microbial Sensitivity Tests
Protein Kinases
Pyrroles
Rhodamines
The fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans.
Article
2013-12-15T00:00:00Z
The fungicide fludioxonil is widely used in agriculture. Residua of this fungicide are occasionally detected in fruits and can therefore be ingested by humans. The human fungal pathogen Candida albicans expresses the target of fludioxonil, Nik1p, a type III histidine kinase involved in stress response. Inhibition of yeast and hyphae growth was hardly observable after treatment of C. albicans SC5314 with fludioxonil. As a side effect, however, we observed a concentration-dependent induction of the expression of the genes CDR1 and CDR2, encoding ATP-binding cassette (ABC) transporters. This was independent of the presence of the target of fludioxonil as induction was also observed in a Δnik1 deletion mutant. Deletion of the CDR1 gene aggravated the inhibition of germ tube formation by fludioxonil, indicating that, in the wild-type, the fungicide was discharged from the cell by Cdr1p. Cdr1p is also known as a resistance factor of C. albicans against the commonly used antimycotic fluconazole. Thus, the effect of concurrent exposure to fludioxonil and known cargoes of ABC transporters on their extrusion and the growth of C. albicans was examined. Pre-incubation with fludioxonil decreased the export rate of rhodamine 6G. The resistance to fluconazole was increased by fludioxonil, independently of Nik1p. Therefore, exposure of C. albicans to fludioxonil may lead to increased resistance to fluconazole treatment.
ORIGINAL
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original manuscript
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2019-08-30 11:32:41.205
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2837732019-08-30T11:36:05Zcom_10033_620533col_10033_620538
Kaba, Hani Ej
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Nimtz, Manfred
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Müller, Peter P
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Bilitewski, Ursula
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2013-04-24T12:06:10Z
2013-04-24T12:06:10Z
2013-01-24
Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicans to iron availability. 2013, 13 (1):16 BMC Microbiol.
1471-2180
23347662
10.1186/1471-2180-13-16
http://hdl.handle.net/10033/283773
BMC microbiology
ABSTRACT: BACKGROUND: Iron is an essential nutrient for almost all organisms, and generating iron limiting conditions for pathogens is one of the host defense strategies against microbial infections. Excess of iron can be toxic; therefore, iron uptake is tightly controlled. The high affinity iron uptake system of the opportunistic pathogenic yeast Candida albicans has been shown to be essential for virulence. Several transcription factors and regulators of iron uptake genes were identified, but the knowledge of signaling pathways is still limited. Gene expression profiling of the Deltahog1 deletion mutant indicated an involvement of the mitogen activated protein (MAP) kinase Hog1p. However, the function of Hog1p in the response of C. albicans to iron availability was not studied in detail. Thus, we analyzed phenotypic and molecular responses of C. albicans to different iron concentrations particularly with respect to the activity of the Hog1p MAP kinase module. RESULTS: We observed flocculation of yeast cells, when the iron ion concentration was equal to or higher than 5 muM. This phenotype was dependent on the MAP kinase Hog1p and the corresponding MAP kinase kinase Pbs2p. Moreover, high extracellular iron ion concentrations led to hyper-phosphorylation of Hog1p. We determined lower amounts of multicopper ferroxidase (MCFO) proteins and lower ferric reductase activity, when the iron ion concentration in the medium was increased. This effect was also observed for the Deltahog1 mutant. However, the amounts of MCFO proteins and the cell surface ferric reductase activity were increased in the Deltahog1 in comparison to wild type cells. This effect was independent of iron availability in growth media. CONCLUSIONS: In C. albicans, the MAP kinase Hog1p is part of the network regulating the response of the organism to iron availability. Hog1p was transiently phosphorylated under high iron concentrations and was essential for a flocculent phenotype. Furthermore, deletion of HOG1 led to increased levels of components of the reductive iron uptake system in comparison to the wild-type, independent of iron concentrations in the media. However, the additional induction of this system by low iron concentrations was independent of HOG1.
ENG
Archived with thanks to BMC microbiology
Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicans to iron availability.
Article
2018-06-13T00:44:42Z
ABSTRACT: BACKGROUND: Iron is an essential nutrient for almost all organisms, and generating iron limiting conditions for pathogens is one of the host defense strategies against microbial infections. Excess of iron can be toxic; therefore, iron uptake is tightly controlled. The high affinity iron uptake system of the opportunistic pathogenic yeast Candida albicans has been shown to be essential for virulence. Several transcription factors and regulators of iron uptake genes were identified, but the knowledge of signaling pathways is still limited. Gene expression profiling of the Deltahog1 deletion mutant indicated an involvement of the mitogen activated protein (MAP) kinase Hog1p. However, the function of Hog1p in the response of C. albicans to iron availability was not studied in detail. Thus, we analyzed phenotypic and molecular responses of C. albicans to different iron concentrations particularly with respect to the activity of the Hog1p MAP kinase module. RESULTS: We observed flocculation of yeast cells, when the iron ion concentration was equal to or higher than 5 muM. This phenotype was dependent on the MAP kinase Hog1p and the corresponding MAP kinase kinase Pbs2p. Moreover, high extracellular iron ion concentrations led to hyper-phosphorylation of Hog1p. We determined lower amounts of multicopper ferroxidase (MCFO) proteins and lower ferric reductase activity, when the iron ion concentration in the medium was increased. This effect was also observed for the Deltahog1 mutant. However, the amounts of MCFO proteins and the cell surface ferric reductase activity were increased in the Deltahog1 in comparison to wild type cells. This effect was independent of iron availability in growth media. CONCLUSIONS: In C. albicans, the MAP kinase Hog1p is part of the network regulating the response of the organism to iron availability. Hog1p was transiently phosphorylated under high iron concentrations and was essential for a flocculent phenotype. Furthermore, deletion of HOG1 led to increased levels of components of the reductive iron uptake system in comparison to the wild-type, independent of iron concentrations in the media. However, the additional induction of this system by low iron concentrations was independent of HOG1.
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2954842019-08-30T11:33:57Zcom_10033_620533col_10033_620538
Hassan, Rabeay Y A
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500
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Helmholtz Centre for Infection Research, Working Group BiSA, Inhoffenstr. 7, 38124 Braunschweig, Germany; Microanalysis Lab, Applied Organic Chemistry Department, National Research Centre (NRC), Eltahrir Street, 12311-Dokki, Cairo, Egypt. Electronic address: rabeayy@yhaoo.com.
2013-07-08T13:36:57Z
2013-07-08T13:36:57Z
2013-05-15
Direct electrochemical determination of Candida albicans activity. 2013, 49C:192-198 Biosens Bioelectron
1873-4235
23747360
10.1016/j.bios.2013.05.015
http://hdl.handle.net/10033/295484
Biosensors & bioelectronics
Despite advances made in the field, rapid detection methods for the human pathogen Candida albicans are still missing. In this regard, bio-electrochemical systems including electrochemical sensors and biosensors satisfy the increasing demand for rapid, reliable, and direct microbial analyses. In this study, the bioelectrochemical characteristics of C. albicans were investigated for use in an analytical system that determines the viability of the organisms. The electrochemical responses of viable and non-viable cells of C. albicans and Saccharomyces cerevisiae were monitored. Cyclic voltammograms (CV) showed an irreversible oxidation peak at about 750mV that accounts for viable cells. The peak current increased at viable cell numbers ranging from 3×10(5) to 1.6×10(7)cells/ml, indicating that the amount of viable cells can be accurately quantified. To elucidate the underlying electron transfer processes, the influence of electron transfer chain (ETC) - inhibitors on the electrochemical behavior of the two organisms were investigated. Inhibition of the function of classical respiratory chain (CRC) led to a decrease in the electrochemical response, whereas the oxidation current increased when the alternative oxidase (AOX) pathway was blocked by salicylhydroxamic acid (SHA). Blocking the AOX pathway improved the electrochemical performance, suggesting an involvement in the CRC, with cytochrome c oxidase (COX) as a relevant protein complex. Mutants, in which components of COX were deleted, showed a lower electro-activity than the wild-type strain. Particularly, deletion of subunit COX5a almost completely abolished the electrochemical signal. We believe that this work can be utilized for the development of early detection assays and opens the door for new technological developments in the field of C. albicans.
ENG
Archived with thanks to Biosensors & bioelectronics
Direct electrochemical determination of Candida albicans activity.
Article
2018-06-12T21:51:20Z
Despite advances made in the field, rapid detection methods for the human pathogen Candida albicans are still missing. In this regard, bio-electrochemical systems including electrochemical sensors and biosensors satisfy the increasing demand for rapid, reliable, and direct microbial analyses. In this study, the bioelectrochemical characteristics of C. albicans were investigated for use in an analytical system that determines the viability of the organisms. The electrochemical responses of viable and non-viable cells of C. albicans and Saccharomyces cerevisiae were monitored. Cyclic voltammograms (CV) showed an irreversible oxidation peak at about 750mV that accounts for viable cells. The peak current increased at viable cell numbers ranging from 3×10(5) to 1.6×10(7)cells/ml, indicating that the amount of viable cells can be accurately quantified. To elucidate the underlying electron transfer processes, the influence of electron transfer chain (ETC) - inhibitors on the electrochemical behavior of the two organisms were investigated. Inhibition of the function of classical respiratory chain (CRC) led to a decrease in the electrochemical response, whereas the oxidation current increased when the alternative oxidase (AOX) pathway was blocked by salicylhydroxamic acid (SHA). Blocking the AOX pathway improved the electrochemical performance, suggesting an involvement in the CRC, with cytochrome c oxidase (COX) as a relevant protein complex. Mutants, in which components of COX were deleted, showed a lower electro-activity than the wild-type strain. Particularly, deletion of subunit COX5a almost completely abolished the electrochemical signal. We believe that this work can be utilized for the development of early detection assays and opens the door for new technological developments in the field of C. albicans.
ORIGINAL
Hassan and Bilitewski.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2974772019-08-30T11:34:22Zcom_10033_620533col_10033_620538
Heintz-Buschart, Anna
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Eickhoff, Holger
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Hohn, Erwin
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Bilitewski, Ursula
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Department of Biological Systems Analysis, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2013-08-07T14:04:32Z
2013-08-07T14:04:32Z
2013-03-10
Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay. 2013, 164 (1):137-42 J. Biotechnol.
1873-4863
23262131
10.1016/j.jbiotec.2012.12.004
http://hdl.handle.net/10033/297477
Journal of biotechnology
Candida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans.
en
Archived with thanks to Journal of biotechnology
Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.
Article
2018-06-13T01:33:13Z
Candida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans.
ORIGINAL
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2019-08-30 11:34:22.372
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/3050742019-08-30T11:30:32Zcom_10033_620533col_10033_620538
El-Mowafy, Mohammed
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Bahgat, Mahmoud M
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Bilitewski, Ursula
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2013-11-07T12:05:13Z
2013-11-07T12:05:13Z
2013-09-17
Deletion of the HAMP domains from the histidine kinase CaNik1p of Candida albicans or treatment with fungicides activates the MAP kinase Hog1p in S. cerevisiae transformants. 2013, 13 (1):209 BMC Microbiol.
1471-2180
24044701
10.1186/1471-2180-13-209
http://hdl.handle.net/10033/305074
BMC microbiology
Microorganisms use two-component signal transduction (TCST) systems to regulate the response of the organism to changes of environmental conditions. Such systems are absent from mammalian cells and are thus of interest as drug targets. Fungal TCST systems are usually composed of a hybrid histidine kinase, comprising the histidine kinase (HisKA) domain and a receiver domain, a histidine phosphotransfer protein and a response regulator. Among the 11 groups of fungal histidine kinases, group III histidine kinases are of particular relevance as they are essential for the activity of different groups of fungicides. A characteristic feature is the N-terminal amino acid repeat domain comprising multiple HAMP domains, of which the function is still largely unknown. In Candida albicans, a fungal human pathogen, three histidine kinases were identified, of which CaNik1p is a group III histidine kinase. Heterologous expression of this protein in Sacchromyces cerevisiae conferred susceptibility to different fungicides. Fungicide activity was associated with phosphorylation of the mitogen activated protein kinase Hog1p.
ENG
Archived with thanks to BMC microbiology
Deletion of the HAMP domains from the histidine kinase CaNik1p of Candida albicans or treatment with fungicides activates the MAP kinase Hog1p in S. cerevisiae transformants.
Article
2018-06-12T23:26:35Z
Microorganisms use two-component signal transduction (TCST) systems to regulate the response of the organism to changes of environmental conditions. Such systems are absent from mammalian cells and are thus of interest as drug targets. Fungal TCST systems are usually composed of a hybrid histidine kinase, comprising the histidine kinase (HisKA) domain and a receiver domain, a histidine phosphotransfer protein and a response regulator. Among the 11 groups of fungal histidine kinases, group III histidine kinases are of particular relevance as they are essential for the activity of different groups of fungicides. A characteristic feature is the N-terminal amino acid repeat domain comprising multiple HAMP domains, of which the function is still largely unknown. In Candida albicans, a fungal human pathogen, three histidine kinases were identified, of which CaNik1p is a group III histidine kinase. Heterologous expression of this protein in Sacchromyces cerevisiae conferred susceptibility to different fungicides. Fungicide activity was associated with phosphorylation of the mitogen activated protein kinase Hog1p.
ORIGINAL
el-mowafy et al_final.pdf
el-mowafy et al_final.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6210542018-06-13T02:46:39Zcom_10033_620533col_10033_620538
Lünsdorf, Heinrich
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-1
Gurramkonda, Chandrasekhar
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-1
Adnan, Ahmad
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-1
Khanna, Navin
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Rinas, Ursula
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2017-08-14T10:15:19Z
2017-08-14T10:15:19Z
2011-06-26
2015-09-04T08:22:20Z
Microbial Cell Factories. 2011 Jun 26;10(1):48
http://dx.doi.org/10.1186/1475-2859-10-48
http://hdl.handle.net/10033/621054
Abstract Background A protective immune response against Hepatitis B infection can be obtained through the administration of a single viral polypeptide, the Hepatitis B surface antigen (HBsAg). Thus, the Hepatitis B vaccine is generated through the utilization of recombinant DNA technology, preferentially by using yeast-based expression systems. However, the polypeptide needs to assemble into spherical particles, so-called virus-like particles (VLPs), to elicit the required protective immune response. So far, no clear evidence has been presented showing whether HBsAg assembles in vivo inside the yeast cell into VLPs or later in vitro during down-stream processing and purification. Results High level production of HBsAg was carried out with recombinant Pichia pastoris using the methanol inducible AOX1 expression system. The recombinant vaccine was isolated in form of VLPs after several down-stream steps from detergent-treated cell lysates. Search for the intracellular localization of the antigen using electron microscopic studies in combination with immunogold labeling revealed the presence of HBsAg in an extended endoplasmic reticulum where it was found to assemble into defined multi-layered, lamellar structures. The distance between two layers was determined as ~6 nm indicating that these lamellas represent monolayers of well-ordered HBsAg subunits. We did not find any evidence for the presence of VLPs within the endoplasmic reticulum or other parts of the yeast cell. Conclusions It is concluded that high level production and intrinsic slow HBsAg VLP assembly kinetics are leading to retention and accumulation of the antigen in the endoplasmic reticulum where it assembles at least partly into defined lamellar structures. Further transport of HBsAg to the Golgi apparatus is impaired thus leading to secretory pathway disfunction and the formation of an extended endoplasmic reticulum which bulges into irregular cloud-shaped formations. As VLPs were not found within the cells it is concluded that the VLP assembly process must take place during down-stream processing after detergent-mediated disassembly of HBsAg lamellas and subsequent reassembly of HBsAg into spherical VLPs.
Virus-like particle production with yeast: ultrastructural and immunocytochemical insights into Pichia pastoris producing high levels of the Hepatitis B surface antigen
Journal Article
en
Lünsdorf et al; licensee BioMed Central Ltd.
2018-06-13T02:46:39Z
Abstract
Background
A protective immune response against Hepatitis B infection can be obtained through the administration of a single viral polypeptide, the Hepatitis B surface antigen (HBsAg). Thus, the Hepatitis B vaccine is generated through the utilization of recombinant DNA technology, preferentially by using yeast-based expression systems. However, the polypeptide needs to assemble into spherical particles, so-called virus-like particles (VLPs), to elicit the required protective immune response. So far, no clear evidence has been presented showing whether HBsAg assembles in vivo inside the yeast cell into VLPs or later in vitro during down-stream processing and purification.
Results
High level production of HBsAg was carried out with recombinant Pichia pastoris using the methanol inducible AOX1 expression system. The recombinant vaccine was isolated in form of VLPs after several down-stream steps from detergent-treated cell lysates. Search for the intracellular localization of the antigen using electron microscopic studies in combination with immunogold labeling revealed the presence of HBsAg in an extended endoplasmic reticulum where it was found to assemble into defined multi-layered, lamellar structures. The distance between two layers was determined as ~6 nm indicating that these lamellas represent monolayers of well-ordered HBsAg subunits. We did not find any evidence for the presence of VLPs within the endoplasmic reticulum or other parts of the yeast cell.
Conclusions
It is concluded that high level production and intrinsic slow HBsAg VLP assembly kinetics are leading to retention and accumulation of the antigen in the endoplasmic reticulum where it assembles at least partly into defined lamellar structures. Further transport of HBsAg to the Golgi apparatus is impaired thus leading to secretory pathway disfunction and the formation of an extended endoplasmic reticulum which bulges into irregular cloud-shaped formations. As VLPs were not found within the cells it is concluded that the VLP assembly process must take place during down-stream processing after detergent-mediated disassembly of HBsAg lamellas and subsequent reassembly of HBsAg into spherical VLPs.
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oai:hzi.openrepository.com:10033/621054
2018-06-13 02:46:39.68
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6207842019-08-30T11:26:12Zcom_10033_620533col_10033_620538
El-Mowafy, Mohammed
b85bc7e644444a1c9f18eb53f69a04d0
500
Bahgat, Mahmoud M
733d5af7dfe4c1b455a00d45c5481fd2
500
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
2017-01-27T11:38:20Z
2017-01-27T11:38:20Z
2013-09-17
2015-09-04T08:26:59Z
BMC Microbiology. 2013 Sep 17;13(1):209
http://dx.doi.org/10.1186/1471-2180-13-209
http://hdl.handle.net/10033/620784
Abstract Background Microorganisms use two-component signal transduction (TCST) systems to regulate the response of the organism to changes of environmental conditions. Such systems are absent from mammalian cells and are thus of interest as drug targets. Fungal TCST systems are usually composed of a hybrid histidine kinase, comprising the histidine kinase (HisKA) domain and a receiver domain, a histidine phosphotransfer protein and a response regulator. Among the 11 groups of fungal histidine kinases, group III histidine kinases are of particular relevance as they are essential for the activity of different groups of fungicides. A characteristic feature is the N-terminal amino acid repeat domain comprising multiple HAMP domains, of which the function is still largely unknown. In Candida albicans, a fungal human pathogen, three histidine kinases were identified, of which CaNik1p is a group III histidine kinase. Heterologous expression of this protein in Sacchromyces cerevisiae conferred susceptibility to different fungicides. Fungicide activity was associated with phosphorylation of the mitogen activated protein kinase Hog1p. Results We have constructed mutated versions of CaNik1p, from which either all HAMP domains were deleted (CaNik1pΔHAMP) or in which the histidine kinase or the receiver domains were not-functional. Expression of CaNIK1ΔHAMP in S. cerevisiae led to severe growth inhibition. Normal growth could be restored by either replacing the phosphate-accepting histidine residue in CaNik1pΔHAMP or by expressing CaNIK1ΔHAMP in S. cerevisiae mutants, in which single genes encoding several components of the HOG pathway were deleted. Expression of proteins with non-functional histidine kinase or receiver domains resulted in complete loss of susceptibility to antifungals, such as fludioxonil. Conditions leading to growth inhibition of transformants also led to phosphorylation of the MAP kinase Hog1p. Conclusion Our results show that functional histidine kinase and receiver domains of CaNik1p were essential for antifungal susceptibility and for activation of the Hog1p. Moreover, for the first time we show that deletion of all HAMP domains from CaNik1p led to activation of Hog1p without an external stimulus. This phenotype was similar to the effects obtained upon treatment with fungicides, as in both cases growth inhibition correlated with Hog1p activation and was dependent on the functionality of the conserved phosphate-accepting histidine residue.
Deletion of the HAMP domains from the histidine kinase CaNik1p of Candida albicans or treatment with fungicides activates the MAP kinase Hog1p in S. cerevisiae transformants
Journal Article
en
El-Mowafy et al.; licensee BioMed Central Ltd.
2018-06-12T18:11:29Z
Abstract
Background
Microorganisms use two-component signal transduction (TCST) systems to regulate the response of the organism to changes of environmental conditions. Such systems are absent from mammalian cells and are thus of interest as drug targets. Fungal TCST systems are usually composed of a hybrid histidine kinase, comprising the histidine kinase (HisKA) domain and a receiver domain, a histidine phosphotransfer protein and a response regulator. Among the 11 groups of fungal histidine kinases, group III histidine kinases are of particular relevance as they are essential for the activity of different groups of fungicides. A characteristic feature is the N-terminal amino acid repeat domain comprising multiple HAMP domains, of which the function is still largely unknown. In Candida albicans, a fungal human pathogen, three histidine kinases were identified, of which CaNik1p is a group III histidine kinase. Heterologous expression of this protein in Sacchromyces cerevisiae conferred susceptibility to different fungicides. Fungicide activity was associated with phosphorylation of the mitogen activated protein kinase Hog1p.
Results
We have constructed mutated versions of CaNik1p, from which either all HAMP domains were deleted (CaNik1pΔHAMP) or in which the histidine kinase or the receiver domains were not-functional. Expression of CaNIK1ΔHAMP in S. cerevisiae led to severe growth inhibition. Normal growth could be restored by either replacing the phosphate-accepting histidine residue in CaNik1pΔHAMP or by expressing CaNIK1ΔHAMP in S. cerevisiae mutants, in which single genes encoding several components of the HOG pathway were deleted. Expression of proteins with non-functional histidine kinase or receiver domains resulted in complete loss of susceptibility to antifungals, such as fludioxonil. Conditions leading to growth inhibition of transformants also led to phosphorylation of the MAP kinase Hog1p.
Conclusion
Our results show that functional histidine kinase and receiver domains of CaNik1p were essential for antifungal susceptibility and for activation of the Hog1p. Moreover, for the first time we show that deletion of all HAMP domains from CaNik1p led to activation of Hog1p without an external stimulus. This phenotype was similar to the effects obtained upon treatment with fungicides, as in both cases growth inhibition correlated with Hog1p activation and was dependent on the functionality of the conserved phosphate-accepting histidine residue.
ORIGINAL
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2019-08-30 11:26:12.951
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5992592019-11-21T13:17:44Zcom_10033_620533col_10033_620538col_10033_620538
Cui, Shuna
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Hassan, Rabeay
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Heintz-Buschart, Anna
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Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2016-02-25T15:46:22Z
2016-02-25T15:46:22Z
2016-01-28
Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein 2016, 21 (2):162 Molecules
1420-3049
26828477
10.3390/molecules21020162
http://hdl.handle.net/10033/599259
Molecules
http://www.mdpi.com/1420-3049/21/2/162
Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein
Article
2018-06-12T17:54:00Z
ORIGINAL
Cui et al.pdf
Cui et al.pdf
Open Access publication
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CC-LICENSE
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license_url
text/plain
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LICENSE
license.txt
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MD5
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TEXT
Cui et al.pdf.txt
Cui et al.pdf.txt
Extracted Text
text/plain
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https://repository.helmholtz-hzi.de/bitstream/10033/599259/6/Cui%20et%20al.pdf.txt
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MD5
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THUMBNAIL
Cui et al.pdf.jpg
Cui et al.pdf.jpg
Generated Thumbnail
image/jpeg
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https://repository.helmholtz-hzi.de/bitstream/10033/599259/7/Cui%20et%20al.pdf.jpg
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10033/599259
oai:repository.helmholtz-hzi.de:10033/599259
2019-11-21 13:17:44.7
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214692019-08-30T11:32:15Zcom_10033_620533col_10033_620538
Neidhardt, Manuel M
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500
Schmitt, Katharina
c3910be9a2580511418a9ced23776201
500
BARO, ANGELIKA
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500
Schneider, Carmen
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500
Bilitewski, Ursula
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500
LASCHAT, SABINE
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500
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-09-05T11:34:44Z
2018-09-05T11:34:44Z
2018-08-08
1463-9084
30043016
10.1039/c8cp03404d
http://hdl.handle.net/10033/621469
The self-assembly of amino acid-derived ionic liquid crystals (ILCs) into lamellar or micellar-like aggregates suggests that they might interact with biological membranes. To get some insight, guanidinium chlorides derived from the natural l-amino acids phenylalanine (Phe), tyrosine (Tyr) and 3,4-dihydroxyphenylalanine (DOPA) were synthesized and their mesomorphic properties were investigated via polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction (SAXS, WAXS). Mesophase types depended on the number of alkoxy side chains. Phe- and Tyr-based ILCs with one and two side chains, respectively, self-assembled into smectic A bilayers (SmA2), while Dopa-derived ILCs with three side chains formed columnar (Colh) mesophases. The mesophase ranges for Phe ILCs increased steadily with side chain length, for Tyr- and Dopa-based ILCs, however, size matching effects were observed. To clarify whether the mesomorphic behaviour has an impact on biological properties, cytotoxic and antibacterial activities of the ILCs were studied. Phe and Tyr ILCs exhibited much higher cytotoxicities (against the L-929 mouse fibroblast cell line) and/or antibacterial activities (against Staphylococcus aureus) than Dopa ILCs, which were mostly inactive. Furthermore, within each series, the side chain length largely influenced the biological activity. Thus, the bulk mesophase behaviour appeared to correlate with the biological properties, in particular, the interactions with membranes, as shown by measuring the intracellular Ca2+ concentration in human monocytic U937 cells after treatment with the amino acid-based ILCs.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Self-assembly and biological activities of ionic liquid crystals derived from aromatic amino acids.
Article
Physical chemistry chemical physics : PCCP
THUMBNAIL
Neidhardt et al.pdf.jpg
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Generated Thumbnail
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TEXT
Neidhardt et al.pdf.txt
Neidhardt et al.pdf.txt
Extracted text
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https://hzi.openrepository.com/bitstream/10033/621469/7/Neidhardt%20et%20al.pdf.txt
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Graphical abstract.pdf.txt
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https://hzi.openrepository.com/bitstream/10033/621469/9/Graphical%20abstract.pdf.txt
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MD5
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Dupplementaey_info.pdf.txt
Dupplementaey_info.pdf.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/621469/11/Dupplementaey_info.pdf.txt
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LICENSE
license.txt
license.txt
text/plain
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CC-LICENSE
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ORIGINAL
Neidhardt et al.pdf
Neidhardt et al.pdf
original manuscript
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MD5
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true
Neidhardt et al.pdf
Neidhardt et al.pdf
original manuscript
application/pdf
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Graphical abstract.pdf
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grafical abstract
application/pdf
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MD5
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Dupplementaey_info.pdf
Dupplementaey_info.pdf
supplementary information
application/pdf
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MD5
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10033/621469
oai:hzi.openrepository.com:10033/621469
2019-08-30 11:32:15.506
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215282019-08-30T11:29:41Zcom_10033_620533col_10033_620538
Götz, Tobias
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500
Schädel, Nicole
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500
Petri, Nadja
7c74afe899e30bbda020dc1bfe55c9f0
500
Kirchhof, Manuel
d15532ba0c53ff8235d763db5234307b
500
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Tovar, Günter E. M.
ffcbba33319a085dcc9f1313dedf4ece
500
Laschat, Sabine
8ac2ae1a75ac9f38b490a368602f33a7
500
Southan, Alexander
c2e2e26f6543e541f804701790d1f39f
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2018-11-01T13:21:22Z
2018-11-01T13:21:22Z
2046-2069
10.1039/C8RA07145D
http://hdl.handle.net/10033/621528
Triazole-based cross-linkers with different spacer lengths and different functional end groups (acrylamides,
methacrylamides, maleimides and vinylsulfonamides) were synthesized, investigated for cytotoxic and
antibacterial activity, and incorporated into poly(acrylamide) (PAAm) and poly(N,N-dimethylacrylamide)
(PDMAAm) hydrogels by free-radical polymerization. Hydrogels prepared with different cross-linkers and
cross-linker contents between 0.2% and 1.0% were compared by gel yields, equilibrium degrees of swelling
(S) and storage moduli (G0). Generally with increasing cross-linker content, G0 values of the hydrogels
increased, while S values decreased. The different polymerizable cross-linker end groups resulted in
a decrease of G0 in the following order for cross-linkers with C4 spacers: acrylamide > maleimide >
methacrylamide > vinylsulfonamide. Longer cross-linker alkyl spacer lengths caused an increase in G0 and
a decrease in S. Independent of the cross-linker used, a universal correlation between G0 and equilibrium
polymer volume fraction f was found. For PAAm hydrogels, G0 ranged between 4 kPa and 23 kPa and f
between 0.07 and 0.14. For PDMAAm hydrogels, G0 ranged between 0.1 kPa and 4.9 kPa and f between
0.02 and 0.06. The collected data were used to establish an empirical model to predict G0 depending on f.
G0 of PAAm and PDMAAm hydrogels is given by G0 ¼ 4034 kPa f2.66 and G0 ¼ 4297 kPa f2.46, respectively.
http://xlink.rsc.org/?DOI=C8RA07145D
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Triazole-based cross-linkers in radical polymerization processes: tuning mechanical properties of poly(acrylamide) and poly( -dimethylacrylamide) hydrogels
Article
8
60
34743
34753
RSC Advances
2018-11-01T13:21:22Z
THUMBNAIL
Götz et al.pdf.jpg
Götz et al.pdf.jpg
Generated Thumbnail
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MD5
6
false
Götz_supplementary.pdf.jpg
Götz_supplementary.pdf.jpg
Generated Thumbnail
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MD5
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TEXT
Götz et al.pdf.txt
Götz et al.pdf.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/621528/5/G%c3%b6tz%20et%20al.pdf.txt
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MD5
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Götz_supplementary.pdf.txt
Götz_supplementary.pdf.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/621528/7/G%c3%b6tz_supplementary.pdf.txt
d5efd0714591f3411dcf07e0d36b4a68
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LICENSE
license.txt
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https://hzi.openrepository.com/bitstream/10033/621528/3/license_rdf
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MD5
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ORIGINAL
Götz et al.pdf
Götz et al.pdf
Open Access publication
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MD5
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Götz_supplementary.pdf
Götz_supplementary.pdf
supplementary information
application/pdf
4719584
https://hzi.openrepository.com/bitstream/10033/621528/2/G%c3%b6tz_supplementary.pdf
1c94d93420944a2f9252e3027f60c53e
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10033/621528
oai:hzi.openrepository.com:10033/621528
2019-08-30 11:29:41.276
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6220262019-11-23T01:59:46Zcom_10033_620533col_10033_620538
Cui, Shuna
da27efd6d737b6cf19a732b10dccf511
500
Hassan, Rabeay
d539d04e38bf4b159998210ebaef5840
500
Heintz-Buschart, Anna
548041a13beb3a165239ec9efaea94a3
500
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2019-11-22T14:47:18Z
2019-11-22T14:47:18Z
2016-01-28
Molecules. 2016 Jan 28;21(2):162. doi: 10.3390/molecules21020162.
1420-3049
26828477
10.3390/molecules21020162
http://hdl.handle.net/10033/622026
Molecules
he severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-α and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Δcos1 and Δsln1 were also observed. Our results thus indicate a new bio-activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans.
en
MDPI AG
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein
Article
21
2
162
2019-11-22T14:47:19Z
THUMBNAIL
Cui et al.pdf.jpg
Cui et al.pdf.jpg
Generated Thumbnail
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92528
https://repository.helmholtz-hzi.de/bitstream/10033/622026/5/Cui%20et%20al.pdf.jpg
a01d0250d5dbd743f5922411dd1d1bad
MD5
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false
TEXT
Cui et al.pdf.txt
Cui et al.pdf.txt
Extracted text
text/plain
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https://repository.helmholtz-hzi.de/bitstream/10033/622026/4/Cui%20et%20al.pdf.txt
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LICENSE
license.txt
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text/plain
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https://repository.helmholtz-hzi.de/bitstream/10033/622026/2/license_rdf
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MD5
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ORIGINAL
Cui et al.pdf
Cui et al.pdf
Open Access publication
application/pdf
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https://repository.helmholtz-hzi.de/bitstream/10033/622026/1/Cui%20et%20al.pdf
f09b550f7c3f85b2f34b0cf9ebc1086f
MD5
1
true
10033/622026
oai:repository.helmholtz-hzi.de:10033/622026
2019-11-23 01:59:46.65
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6222052020-03-14T01:59:39Zcom_10033_620533col_10033_620538
Westerhausen, Sibel
e8b7b29ce1ec290546a67f4771e2532a
300
Nowak, Melanie
7f75ad60672f3070fffcbd64ef137b5a
300
Torres-Vargas, Claudia E
eac6cbd7f3bba2ecf280c8b24bc70f99
300
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Bohn, Erwin
949d560d14d84d5b0cf76c3e4110faa9
300
Grin, Iwan
79c8e3d2c46a4ca0c82a0ea3e248b95b
300
Wagner, Samuel
d5e8efaf7f2bb0b839e9abf820494a22
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-03-13T10:23:53Z
2020-03-13T10:23:53Z
2020-02-18
Mol Microbiol. 2020 Feb 18. doi: 10.1111/mmi.14490.
32068313
10.1111/mmi.14490
http://hdl.handle.net/10033/622205
1365-2958
Molecular microbiology
The elucidation of the molecular mechanisms of secretion through bacterial protein secretion systems is impeded by a shortage of assays to quantitatively assess secretion kinetics. Also the analysis of the biological role of these secretion systems as well as the identification of inhibitors targeting these systems would greatly benefit from the availability of a simple, quick and quantitative assay to monitor principle secretion and injection into host cells. Here, we present a versatile solution to this need, utilizing the small and very bright NanoLuc luciferase to assess the function of the type III secretion system encoded by Salmonella pathogenicity island 1. Type III secretion substrate-NanoLuc fusions are readily secreted into the culture supernatant, where they can be quantified by luminometry after removal of bacteria. The NanoLuc-based secretion assay features a very high signal-to-noise ratio and sensitivity down to the nanolitre scale. The assay enables monitoring of secretion kinetics and is adaptable to a high throughput screening format in 384-well microplates. We further developed a split NanoLuc-based assay that enables the real-time monitoring of type III secretion-dependent injection of effector-HiBiT fusions into host cells stably expressing the complementing NanoLuc-LgBiT.
en
Wiley
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Salmonella
Luciferase
Type III secretion system
effector proteins
protein injection
protein secretion
A NanoLuc luciferase-based assay enabling the real-time analysis of protein secretion and injection by bacterial type III secretion systems.
Article
Molecular microbiology
England
2020-03-13T10:23:53Z
THUMBNAIL
Westerhausen et al.pdf.jpg
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Westerhausen et al.pdf.txt
Westerhausen et al.pdf.txt
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license.txt
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Westerhausen et al.pdf
Westerhausen et al.pdf
Open Access article
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https://repository.helmholtz-hzi.de/bitstream/10033/622205/1/Westerhausen%20et%20al.pdf
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10033/622205
oai:repository.helmholtz-hzi.de:10033/622205
2020-03-14 01:59:39.575
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-05-13T13:35:25Z
2020-05-13T13:35:25Z
2020-04-15
mSphere. 2020 Apr 15;5(2). pii: 5/2/e00016-20. doi: 10.1128/mSphere.00016-20.
32295866
10.1128/mSphere.00016-20
http://hdl.handle.net/10033/622261
2379-5042
mSphere
Candida albicans adapts to various conditions in different body niches by regulating gene expression, protein synthesis, and metabolic pathways. These adaptive reactions not only allow survival but also influence the interaction with host cells, which is governed by the composition and structure of the fungal cell wall. Numerous studies had shown linkages between mitochondrial functionality, cell wall integrity and structure, and pathogenicity. Thus, we decided to inhibit single complexes of the respiratory chain of C. albicans and to analyze the resultant interaction with macrophages via their phagocytic activity. Remarkably, inhibition of the fungal bc1 complex by antimycin A increased phagocytosis, which correlated with an increased accessibility of β-glucans. To contribute to mechanistic insights, we performed metabolic studies, which highlighted significant changes in the abundance of constituents of the plasma membrane. Collectively, our results reinforce the strong linkage between fungal energy metabolism and other components of fungal physiology, which also determine the vulnerability to immune defense reactions.IMPORTANCE The yeast Candida albicans is one of the major fungal human pathogens, for which new therapeutic approaches are required. We aimed at enhancements of the phagocytosis efficacy of macrophages by targeting the cell wall structure of C. albicans, as the coverage of the β-glucan layer by mannans is one of the immune escape mechanisms of the fungus. We unambiguously show that inhibition of the fungal bc1 complex correlates with increased accessibilities of β-glucans and improved phagocytosis efficiency. Metabolic studies proved not only the known direct effects on reactive oxygen species (ROS) production and fermentative pathways but also the clear downregulation of the ergosterol pathway and upregulation of unsaturated fatty acids. The changed composition of the plasma membrane could also influence the interaction with the overlying cell wall. Thus, our work highlights the far-reaching relevance of energy metabolism, indirectly also for host-pathogen interactions, without affecting viability.
en
ASM
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
antimycin A
complex III
metabolism
phagocytosis
respiratory chain
Inhibition of Respiration of Candida albicans by Small Molecules Increases Phagocytosis Efficacy by Macrophages.
Article
5
2
mSphere
United States
2020-05-13T13:35:25Z
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oai:repository.helmholtz-hzi.de:10033/622261
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222602020-05-14T01:36:30Zcom_10033_620533col_10033_620538
Cui, Shuna
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstraße 7, 38124 Braunschweig, Germany.
2020-05-13T13:32:11Z
2020-05-13T13:32:11Z
2020-04-15
mSphere. 2020 Apr 15;5(2). pii: 5/2/e00016-20. doi: 10.1128/mSphere.00016-20.
32295866
10.1128/mSphere.00016-20
http://hdl.handle.net/10033/622260
2379-5042
mSphere
Candida albicans adapts to various conditions in different body niches by regulating gene expression, protein synthesis, and metabolic pathways. These adaptive reactions not only allow survival but also influence the interaction with host cells, which is governed by the composition and structure of the fungal cell wall. Numerous studies had shown linkages between mitochondrial functionality, cell wall integrity and structure, and pathogenicity. Thus, we decided to inhibit single complexes of the respiratory chain of C. albicans and to analyze the resultant interaction with macrophages via their phagocytic activity. Remarkably, inhibition of the fungal bc1 complex by antimycin A increased phagocytosis, which correlated with an increased accessibility of β-glucans. To contribute to mechanistic insights, we performed metabolic studies, which highlighted significant changes in the abundance of constituents of the plasma membrane. Collectively, our results reinforce the strong linkage between fungal energy metabolism and other components of fungal physiology, which also determine the vulnerability to immune defense reactions.IMPORTANCE The yeast Candida albicans is one of the major fungal human pathogens, for which new therapeutic approaches are required. We aimed at enhancements of the phagocytosis efficacy of macrophages by targeting the cell wall structure of C. albicans, as the coverage of the β-glucan layer by mannans is one of the immune escape mechanisms of the fungus. We unambiguously show that inhibition of the fungal bc1 complex correlates with increased accessibilities of β-glucans and improved phagocytosis efficiency. Metabolic studies proved not only the known direct effects on reactive oxygen species (ROS) production and fermentative pathways but also the clear downregulation of the ergosterol pathway and upregulation of unsaturated fatty acids. The changed composition of the plasma membrane could also influence the interaction with the overlying cell wall. Thus, our work highlights the far-reaching relevance of energy metabolism, indirectly also for host-pathogen interactions, without affecting viability.
en
American Society of Microbiology
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
antimycin A
complex III
metabolism
phagocytosis
respiratory chain
Inhibition of Respiration of Candida albicans by Small Molecules Increases Phagocytosis Efficacy by Macrophages.
Article
5
2
mSphere
United States
2020-05-13T13:32:12Z
THUMBNAIL
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Cui et al.pdf
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oai:repository.helmholtz-hzi.de:10033/622260
2020-05-14 01:36:30.811
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6223772020-08-04T02:35:32Zcom_10033_620533col_10033_620538
Zapol'skii, Viktor A
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Kaufmann, Dieter E
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-08-03T13:16:56Z
2020-08-03T13:16:56Z
2020-06-21
Molecules. 2020;25(12):2863. Published 2020 Jun 21. doi:10.3390/molecules25122863.
32575902
10.3390/molecules25122863
http://hdl.handle.net/10033/622377
1420-3049
Molecules (Basel, Switzerland)
Substituted nitrogen heterocycles are structural key units in many important pharmaceuticals. A new synthetic approach towards heterocyclic compounds displaying antibacterial activity against Staphylococcus aureus or cytotoxic activity has been developed. The selective synthesis of a series of 64 new N-heterocycles from the three nitrobutadienes 2-nitroperchloro-1,3-butadiene, 4-bromotetrachloro-2-nitro-1,3-butadiene and (Z)-1,1,4-trichloro-2,4-dinitrobuta-1,3-diene proved feasible. Their reactions with N-, O- and S-nucleophiles provide rapid access to push-pull substituted benzoxazolines, benzimidazolines, imidazolidines, thiazolidinones, pyrazoles, pyrimidines, pyridopyrimidines, benzoquinolines, isothiazoles, dihydroisoxazoles, and thiophenes with unique substitution patterns. Antibacterial activities of 64 synthesized compounds were examined. Additionally, seven compounds (thiazolidinone, nitropyrimidine, indole, pyridopyrimidine, and thiophene derivatives) exhibited a significant cytotoxicity with IC50-values from 1.05 to 20.1 µM. In conclusion, it was demonstrated that polyhalonitrobutadienes have an interesting potential as structural backbones for a variety of highly functionalized, pharmaceutically active heterocycles.
en
MDPI
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
heterocyclization
medicinal chemistry
nitrogen heterocycles
nucleophilic substitution
polyhalonitrobutadienes
Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds.
Article
25
12
Molecules (Basel, Switzerland)
Switzerland
2020-08-03T13:16:57Z
THUMBNAIL
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Zapol’skii et al.pdf.jpg
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Zapol’skii et al.pdf.txt
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LICENSE
license.txt
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ORIGINAL
Zapol’skii et al.pdf
Zapol’skii et al.pdf
Open Access publication
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true
10033/622377
oai:repository.helmholtz-hzi.de:10033/622377
2020-08-04 02:35:32.121
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6224912020-10-01T03:02:55Zcom_10033_620533col_10033_620538
Icik, Esra
ae584fbb5fe8064b3fe2bf90ff78191a
300
Jolly, Anthony
4b919279a02d02e7218c03ecf794de4b
300
Löffler, Paul
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300
Agelidis, Nektarios
9406ae694eeda4d62a5ad50ee16258c8
300
Bugdayci, Bakiye
d750499304add06ffe2d0271fbd2d71b
300
Altevogt, Luca
cb2f61f7772236c582a9584d6b580619
300
Bilitewski, Ursula
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Baro, Angelika
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LASCHAT, SABINE
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500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-09-30T12:59:45Z
2020-09-30T12:59:45Z
2020-08-10
Eur J Org Chem 2020;2020(33):5368-5379 doi:10.1002/ejoc.202000811.
1434-193X
10.1002/ejoc.202000811
http://hdl.handle.net/10033/622491
European Journal of Organic Chemistry
Three N‐Boc‐protected amino acids, l‐serine, l‐aspartic, and l‐glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann‐Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu‐catalyzed click reaction provided a library of amino acid based triazoles, which were further N‐methylated to triazolium iodides or deprotected and precipitated as free amino acid triazole dihydrochlorides. The biological properties of all derivatives were investigated by cytotoxicity assay (against L929 mouse fibroblasts) and broth microdilution method (E. coli ΔTolC and S. aureus). First results reveal complete inactivity for triazolium iodides with cell viabilities and microbial growths nearly 100 %, indicating them as possible analogs of advanced glycation endproducts (AGEs).
en
Wiley-VCH
Attribution-NonCommercial-ShareAlike 4.0 International
http://doi.wiley.com/10.1002/tdm_license_1.1
http://creativecommons.org/licenses/by-nc-sa/4.0/
Physical and Theoretical Chemistry
Organic Chemistry
Synthesis and Biological Evaluation of a Library of AGE-Related Amino Acid Triazole Crosslinkers
Article
European Journal of Organic Chemistry
2020-09-30T12:59:46Z
THUMBNAIL
Icik et al.pdf.jpg
Icik et al.pdf.jpg
Generated Thumbnail
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MD5
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Icik_supmat.pdf.jpg
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Generated Thumbnail
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MD5
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TEXT
Icik et al.pdf.txt
Icik et al.pdf.txt
Extracted text
text/plain
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66716d62797d40ff5b3d9b48fe2a494b
MD5
5
false
Icik_supmat.pdf.txt
Icik_supmat.pdf.txt
Extracted text
text/plain
58707
https://repository.helmholtz-hzi.de/bitstream/10033/622491/7/Icik_supmat.pdf.txt
fea11277120e4c9dde38ce594e5610f7
MD5
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LICENSE
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text/plain
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ORIGINAL
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Icik et al.pdf
Open Access publication
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MD5
1
true
Icik_supmat.pdf
Icik_supmat.pdf
supporting materials
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f86f7155b65791137fa566a8cd106fb4
MD5
2
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10033/622491
oai:repository.helmholtz-hzi.de:10033/622491
2020-10-01 03:02:55.679
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6226032020-11-24T01:42:17Zcom_10033_620533col_10033_620538
Seubert, Philipp
32f5834bf22c9fbe85733b81af53ca33
300
Freund, Marcel
4363b0167dabfe15d8fc53e55d6205e2
300
Rudolf, Richard
e335b9c9646668f769e01055db0bd641
300
Lin, Yulin
752dedddabe248bcfc5b91bcccd03684
300
Altevogt, Luca
cb2f61f7772236c582a9584d6b580619
500
Bilitewski, Ursula
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500
Baro, Angelika
26fe58e8ecef638183ee30f11e51345d
500
Laschat, Sabine
8ac2ae1a75ac9f38b490a368602f33a7
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-11-23T08:38:04Z
2020-11-23T08:38:04Z
2020-07-22
Synlett 2020 31 12 doi: 10.1055/s-0040-1707810.
09365214
10.1055/s-0040-1707810
http://hdl.handle.net/10033/622603
14372096
Synlett
2-s2.0-85087912934
SCOPUS_ID:85087912934
The reaction of 2-chloro-3-nitroquinoline and a series of amines and aminoalkanoates under
basic microwave-mediated conditions and Buchwald-Hartwig amination conditions is
reported. The microwave irradiation favored the reaction with amines, resulting in yields up to
80%, while amino acid functionalization gave yields comparable to those of BuchwaldHartwig amination. (2R)-4-[(6,7-dimethoxy-3-nitroquinolinyl)amino]-2-hydroxybutanoate
could be successfully cyclized to the pyoverdin chromophore, a subunit of siderophores.
Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
en
Thieme Verlag
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Amination
aminonitroquinolines
Buchwald-Hartwig amination
microwave heating
pyoverdins
siderophores
Buchwald-Hartwig versus Microwave-Assisted Amination of Chloroquinolines: En Route to the Pyoverdin Chromophore
Article
31
12
1177
1181
Synlett
THUMBNAIL
2021-05-18
Seubert et al.pdf.jpg
Seubert et al.pdf.jpg
Generated Thumbnail
image/jpeg
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MD5
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2021-05-18
Seubert_supp.pdf.jpg
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Generated Thumbnail
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MD5
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TEXT
2021-05-18
Seubert et al.pdf.txt
Seubert et al.pdf.txt
Extracted text
text/plain
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MD5
5
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2021-05-18
Seubert_supp.pdf.txt
Seubert_supp.pdf.txt
Extracted text
text/plain
47542
https://repository.helmholtz-hzi.de/bitstream/10033/622603/7/Seubert_supp.pdf.txt
7ae48f6509aa6076c5cceab424fbe679
MD5
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LICENSE
license.txt
license.txt
text/plain
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cb598eeb10bfed09d26fd8d285172ad4
MD5
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CC-LICENSE
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MD5
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ORIGINAL
Seubert et al.pdf
Seubert et al.pdf
original manuscript
application/pdf
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https://repository.helmholtz-hzi.de/bitstream/10033/622603/1/Seubert%20et%20al.pdf
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MD5
1
true
Seubert_supp.pdf
Seubert_supp.pdf
supplementary materials
application/pdf
5431274
https://repository.helmholtz-hzi.de/bitstream/10033/622603/2/Seubert_supp.pdf
214f3b03657c159fc558f582f26dbc11
MD5
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10033/622603
oai:repository.helmholtz-hzi.de:10033/622603
2020-11-24 01:42:17.807
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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