2024-03-28T08:08:21Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/6214042019-08-30T11:25:06Zcom_10033_620968col_10033_621182
Wheeler, Nicole E
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500
Gardner, Paul P
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Barquist, Lars
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500
HIRI, Helmoltz-Institut für RNA-basierteInfektionsforschung, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
2018-06-18T13:59:04Z
2018-06-18T13:59:04Z
2018-01-01
1553-7404
29738521
10.1371/journal.pgen.1007333
http://hdl.handle.net/10033/621404
Emerging pathogens are a major threat to public health, however understanding how pathogens adapt to new niches remains a challenge. New methods are urgently required to provide functional insights into pathogens from the massive genomic data sets now being generated from routine pathogen surveillance for epidemiological purposes. Here, we measure the burden of atypical mutations in protein coding genes across independently evolved Salmonella enterica lineages, and use these as input to train a random forest classifier to identify strains associated with extraintestinal disease. Members of the species fall along a continuum, from pathovars which cause gastrointestinal infection and low mortality, associated with a broad host-range, to those that cause invasive infection and high mortality, associated with a narrowed host range. Our random forest classifier learned to perfectly discriminate long-established gastrointestinal and invasive serovars of Salmonella. Additionally, it was able to discriminate recently emerged Salmonella Enteritidis and Typhimurium lineages associated with invasive disease in immunocompromised populations in sub-Saharan Africa, and within-host adaptation to invasive infection. We dissect the architecture of the model to identify the genes that were most informative of phenotype, revealing a common theme of degradation of metabolic pathways in extraintestinal lineages. This approach accurately identifies patterns of gene degradation and diversifying selection specific to invasive serovars that have been captured by more labour-intensive investigations, but can be readily scaled to larger analyses.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella enterica.
Article
PLoS genetics
2018-06-18T13:59:04Z
ORIGINAL
Wheeler et al.pdf
Wheeler et al.pdf
Open Access puplication
application/pdf
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https://hzi.openrepository.com/bitstream/10033/621404/1/Wheeler%20et%20al.pdf
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Wheeler et al.pdf.txt
Wheeler et al.pdf.txt
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THUMBNAIL
Wheeler et al.pdf.jpg
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Generated Thumbnail
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10033/621404
oai:hzi.openrepository.com:10033/621404
2019-08-30 11:25:06.617
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214382019-08-30T11:33:54Zcom_10033_620968col_10033_621182
Cain, Amy K
adf16e6ff6ffcec6ab2733b61bc2095e
500
Boinett, Christine J
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500
Barquist, Lars
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500
Dordel, Janina
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500
Fookes, Maria
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500
Mayho, Matthew
84c5825782d32975733b358dd1c57c95
500
Ellington, Matthew J
b3a49b522bdd6a0c6eea1eb9edb76892
500
Goulding, David
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500
Pickard, Derek
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500
Wick, Ryan R
93d792995e3ec5440117459b4901e857
500
Holt, Kathryn E
c12a9a04e7fadac934f3484421e6298a
500
Parkhill, Julian
2725d4556af2a8c6288bb04de62173dd
500
Thomson, Nicholas R
6807d36a4b99b463429e3dbab27502b8
500
HIRI, Helmoltz-Institut für RNA-basierteInfektionsforschung, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
2018-08-07T09:45:02Z
2018-08-07T09:45:02Z
2018-06-29
2045-2322
29959380
10.1038/s41598-018-28199-y
http://hdl.handle.net/10033/621438
Colistin remains one of the few antibiotics effective against multi-drug resistant (MDR) hospital pathogens, such as Klebsiella pneumoniae. Yet resistance to this last-line drug is rapidly increasing. Characterized mechanisms of col
en
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin.
Article
Scientific reports
2018-08-07T09:45:04Z
ORIGINAL
Cain et al.pdf
Cain et al.pdf
Open Access publication
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Cain et al.pdf.txt
Cain et al.pdf.txt
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THUMBNAIL
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10033/621438
oai:hzi.openrepository.com:10033/621438
2019-08-30 11:33:54.38
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215852019-08-30T11:28:46Zcom_10033_620968col_10033_621182
Nolan, Laura M
2b0ce6099ef70dcaf757bceeb333520c
500
Whitchurch, Cynthia B
bf25e28b0338738dba7db7fbdc8b495f
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Katrib, Marilyn
506947564e55b10fc28d0fa464a232d8
500
Boinett, Christine J
c0d46ef3ba063e9c1bab1e1e94bf0156
500
Mayho, Matthew
84c5825782d32975733b358dd1c57c95
500
Goulding, David
59ecae622eb965d1f35068ddc194a7a1
500
Charles, Ian G
be213d723082db18b76511afe819ce74
500
Filloux, Alain
c0532127bb42ce89887460dca7f961f0
500
Parkhill, Julian
2725d4556af2a8c6288bb04de62173dd
500
Cain, Amy K
adf16e6ff6ffcec6ab2733b61bc2095e
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2018-11-27T12:42:20Z
2018-11-27T12:42:20Z
2018-11-01
2057-5858
30383525
10.1099/mgen.0.000229
http://hdl.handle.net/10033/621585
Pseudomonas aeruginosa is an extremely successful pathogen able to cause both acute and chronic infections in a range of hosts, utilizing a diverse arsenal of cell-associated and secreted virulence factors. A major cell-associated virulence factor, the Type IV pilus (T4P), is required for epithelial cell adherence and mediates a form of surface translocation termed twitching motility, which is necessary to establish a mature biofilm and actively expand these biofilms. P. aeruginosa twitching motility-mediated biofilm expansion is a coordinated, multicellular behaviour, allowing cells to rapidly colonize surfaces, including implanted medical devices. Although at least 44 proteins are known to be involved in the biogenesis, assembly and regulation of the T4P, with additional regulatory components and pathways implicated, it is unclear how these components and pathways interact to control these processes. In the current study, we used a global genomics-based random-mutagenesis technique, transposon directed insertion-site sequencing (TraDIS), coupled with a physical segregation approach, to identify all genes implicated in twitching motility-mediated biofilm expansion in P. aeruginosa. Our approach allowed identification of both known and novel genes, providing new insight into the complex molecular network that regulates this process in P. aeruginosa. Additionally, our data suggest that the flagellum-associated gene products have a differential effect on twitching motility, based on whether components are intra- or extracellular. Overall the success of our TraDIS approach supports the use of this global genomic technique for investigating virulence genes in bacterial pathogens.
Microbiology Society
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
A global genomic approach uncovers novel components for twitching motility-mediated biofilm expansion in Pseudomonas aeruginosa.
Article
Microbial genomics
2018-11-27T12:42:21Z
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Nolan et al.pdf.txt
Nolan et al.pdf.txt
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ORIGINAL
Nolan et al.pdf
Nolan et al.pdf
Open Access article
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MD5
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supplementl material_1.pdf
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supplemental figures S1 to S3
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supplemental material_2.xlsx
supplemental material_2.xlsx
supplemental table S4
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10033/621585
oai:hzi.openrepository.com:10033/621585
2019-08-30 11:28:46.292
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6216202019-08-30T11:30:55Zcom_10033_620968col_10033_621182
Kingsley, Robert A
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Langridge, Gemma
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Smith, Sarah E
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Makendi, Carine
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Fookes, Maria
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Wileman, Tom M
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El Ghany, Moataz Abd
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Keith Turner, A
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Dyson, Zoe A
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Sridhar, Sushmita
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Pickard, Derek
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Kay, Sally
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Feasey, Nicholas
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Wong, Vanessa
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Barquist, Lars
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Dougan, Gordon
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HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2018-12-19T11:44:21Z
2018-12-19T11:44:21Z
2018-11-18
1462-2920
30450829
10.1111/1462-2920.14458
http://hdl.handle.net/10033/621620
Contaminated water is a major risk factor associated with the transmission of Salmonella enterica serovar Typhi (S. Typhi), the aetiological agent of human typhoid. However, little is known about how this pathogen adapts to living in the aqueous environment. We used transcriptome analysis (RNA-seq) and transposon mutagenesis (TraDIS) to characterize these adaptive changes and identify multiple genes that contribute to survival. Over half of the genes in the S. Typhi genome altered expression level within the first 24 h following transfer from broth culture to water, although relatively few did so in the first 30 min. Genes linked to central metabolism, stress associated with arrested proton motive force and respiratory chain factors changed expression levels. Additionally, motility and chemotaxis genes increased expression, consistent with a scavenging lifestyle. The viaB-associated gene tviC encoding a glcNAc epimerase that is required for Vi polysaccharide biosynthesis was, along with several other genes, shown to contribute to survival in water. Thus, we define regulatory adaptation operating in S. Typhi that facilitates survival in water.
Wiley-Blackwell
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Functional analysis of Salmonella Typhi adaptation to survival in water.
Article
Environmental microbiology
2018-12-19T11:44:22Z
THUMBNAIL
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Kingsley et al.pdf.jpg
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Kingsley et al.pdf.txt
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ORIGINAL
Kingsley et al.pdf
Kingsley et al.pdf
Open Access article
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10033/621620
oai:hzi.openrepository.com:10033/621620
2019-08-30 11:30:55.215
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6217972019-08-30T11:36:28Zcom_10033_620968col_10033_621182
Jose, Bethany R
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500
Gardner, Paul P
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500
Barquist, Lars
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500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2019-06-04T12:51:12Z
2019-06-04T12:51:12Z
2019-04-30
Biochem Soc Trans. 2019 Apr 30;47(2):527-539. doi: 10.1042/BST20180171. Epub 2019 Mar 5.
1470-8752
30837318
10.1042/BST20180171
http://hdl.handle.net/10033/621797
Biochemical Society Transactions
Understanding how new genes originate and integrate into cellular networks is key to understanding evolution. Bacteria present unique opportunities for both the natural history and experimental study of gene origins, due to their large effective population sizes, rapid generation times, and ease of genetic manipulation. Bacterial small non-coding RNAs (sRNAs), in particular, many of which operate through a simple antisense regulatory logic, may serve as tractable models for exploring processes of gene origin and adaptation. Understanding how and on what timescales these regulatory molecules arise has important implications for understanding the evolution of bacterial regulatory networks, in particular, for the design of comparative studies of sRNA function. Here, we introduce relevant concepts from evolutionary biology and review recent work that has begun to shed light on the timescales and processes through which non-functional transcriptional noise is co-opted to provide regulatory functions. We explore possible scenarios for sRNA origin, focusing on the co-option, or exaptation, of existing genomic structures which may provide protected spaces for sRNA evolution.
en
Portland Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
bacteria
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500
exaptation
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ncRNA
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sRNAs
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selection
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transcriptional noise
07394d1b-c58a-4afa-bd46-c3adcb27f47b
Transcriptional noise and exaptation as sources for bacterial sRNAs.
Article
Biochemical Society transactions
THUMBNAIL
2020-03-05
Jose, Gardner and Barquist.pdf.jpg
Jose, Gardner and Barquist.pdf.jpg
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TEXT
2020-03-05
Jose, Gardner and Barquist.pdf.txt
Jose, Gardner and Barquist.pdf.txt
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MD5
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LICENSE
license.txt
license.txt
text/plain
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CC-LICENSE
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ORIGINAL
Jose, Gardner and Barquist.pdf
Jose, Gardner and Barquist.pdf
original manuscript
application/pdf
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https://hzi.openrepository.com/bitstream/10033/621797/1/Jose%2c%20Gardner%20and%20Barquist.pdf
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10033/621797
oai:hzi.openrepository.com:10033/621797
2019-08-30 11:36:28.737
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6218562019-08-30T11:26:09Zcom_10033_620968col_10033_621182col_10033_620969
Holmqvist, Erik
f725b00733ee3846d2ab24e72b565408
500
Li, Lei
955ea5d8e20f03db729c64dff0425af4
500
Bischler, Thorsten
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500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Vogel, Jörg
1a02c431c2bec6d54e2051b4abdf4176
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2019-07-10T08:45:54Z
2019-07-10T08:45:54Z
2018-06-07
Mol Cell. 2018 Jun 7;70(5):971-982.e6. doi: 10.1016/j.molcel.2018.04.017. Epub 2018 May 24.
1097-4164
29804828
10.1016/j.molcel.2018.04.017
http://hdl.handle.net/10033/621856
Molecular Cell
The conserved RNA-binding protein ProQ has emerged as the centerpiece of a previously unknown third large network of post-transcriptional control in enterobacteria. Here, we have used in vivo UV crosslinking and RNA sequencing (CLIP-seq) to map hundreds of ProQ binding sites in Salmonella enterica and Escherichia coli. Our analysis of these binding sites, many of which are conserved, suggests that ProQ recognizes its cellular targets through RNA structural motifs found in small RNAs (sRNAs) and at the 3′ end of mRNAs. Using the cspE mRNA as a model for 3′ end targeting, we reveal a function for ProQ in protecting mRNA against exoribonucleolytic activity. Taken together, our results underpin the notion that ProQ governs a post-transcriptional network distinct from those of the well-characterized sRNA-binding proteins, CsrA and Hfq, and suggest a previously unrecognized, sRNA-independent role of ProQ in stabilizing mRNAs.
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
3′ UTR
CLIP-seq
ProQ
RNA-binding protein
exoribonuclease
post-transcriptional control
Global Maps of ProQ Binding In Vivo Reveal Target Recognition via RNA Structure and Stability Control at mRNA 3' Ends.
Article
Molecular cell
2019-07-10T08:45:54Z
THUMBNAIL
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10033/621856
oai:hzi.openrepository.com:10033/621856
2019-08-30 11:26:09.992
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6218772019-08-30T11:24:28Zcom_10033_620968col_10033_621182
Ondari, Edna M
a4c72b78df79dc9f31b553713189b8da
500
Klemm, Elizabeth J
f1d9b50739ae3b637359a94b9e879200
500
Msefula, Chisomo L
24b4ed09f10b51ac9960a731d0b6eac6
500
El Ghany, Moataz Abd
fb92304db44a563654ad7f11890e7968
500
Heath, Jennifer N
d4d6b81723d8af9fbc7868c235777bd1
500
Pickard, Derek J
58bb5e875eca2293adba957668a2addd
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Dougan, Gordon
0dacb9198028a80fdb992d8d31a44b34
500
Kingsley, Robert A
7c15bf36e48845cdbd87e09b0a24f05f
500
MacLennan, Calman A
d25464454925ad6776729743922f7ce0
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2019-07-16T07:55:59Z
2019-07-16T07:55:59Z
2019-01-01
Wellcome Open Res. 2019 Apr 25;4:74. doi: 10.12688/wellcomeopenres.15059.1. eCollection 2019.
2398-502X
31231691
10.12688/wellcomeopenres.15059.1
http://hdl.handle.net/10033/621877
Wellcome Open Research
Background: Salmonella Typhimurium ST313 exhibits signatures of adaptation to invasive human infection, including higher resistance to humoral immune responses than gastrointestinal isolates. Full resistance to antibody-mediated complement killing (serum resistance) among nontyphoidal Salmonellae is uncommon, but selection of highly resistant strains could compromise vaccine-induced antibody immunity. Here, we address the hypothesis that serum resistance is due to a distinct genotype or transcriptome response in S. Typhimurium ST313. Methods: Six S. Typhimurium ST313 bloodstream isolates, three of which were antibody resistant, were studied. Genomic content (single nucleotide polymorphisms and larger chromosomal modifications) of the strains was determined by Illumina and PACBIO sequencing, and functionally characterized using RNA-seq, transposon directed insertion site sequencing (TraDIS), targeted gene deletion and transfer of selected point mutations in an attempt to identify features associated with serum resistance. Results: Sequence polymorphisms in genes from strains with atypical serum susceptibility when transferred from strains that were highly resistant or susceptible to a strain that exhibited intermediate susceptibility did not significantly alter serum killing phenotype. No large chromosomal modifications typified serum resistance or susceptibility. Genes required for resistance to serum identified by TraDIS and RNA-seq included those involved in exopolysaccharide synthesis, iron scavenging and metabolism. Most of the down-regulated genes were associated with membrane proteins. Resistant and susceptible strains had distinct transcriptional responses to serum, particularly related to genes responsible for polysaccharide biosynthesis. There was higher upregulation of wca locus genes, involved in the biosynthesis of colanic acid exopolysaccharide, in susceptible strains and increased expression of fepE, a regulator of very long-chain lipopolysaccharide in resistant strains. Conclusion: Clinical isolates of S. Typhimurium ST313 exhibit distinct antibody susceptibility phenotypes that may be associated with changes in gene expression on exposure to serum.
F1000Research
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Invasive salmonellosis
antibody
complement
genome
serum resistance
transcriptome
Rapid transcriptional responses to serum exposure are associated with sensitivity and resistance to antibody-mediated complement killing in invasive Typhimurium ST313.
Article
Wellcome open research
2019-07-16T07:55:59Z
THUMBNAIL
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Ondari et al.pdf
Ondari et al.pdf
Open Access publication
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10033/621877
oai:hzi.openrepository.com:10033/621877
2019-08-30 11:24:28.727
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6223552020-07-23T01:24:36Zcom_10033_620968col_10033_621182col_10033_620969col_10033_621391
Mika-Gospodorz, Bozena
07c26a298d8e1b0a0890be29073a6831
300
Giengkam, Suparat
582a01e6a7f3cf003512aabe4cf847c8
300
Westermann, Alexander J
afd7dc94c1dc4b1cefd28cc18f09916e
Wongsantichon, Jantana
761e813446b52e525c6e5e7dbdcec4fa
300
Kion-Crosby, Willow
3d60d1b14b7f5c292d6afdd7a0472446
300
Chuenklin, Suthida
c05f10d05e3d401eca4c753bc4158c82
300
Wang, Loo Chien
b4ce7b0d651528c8d48eef6e809f3c9b
300
Sunyakumthorn, Piyanate
70c249cd9be56252bb39f53275744f9d
300
Sobota, Radoslaw M
4bfa65afa2810f64a52d9e9fc40c56d0
300
Subbian, Selvakumar
95ce9fd7882847ea5c6a3ae80bd0e621
300
Vogel, Jörg
1a02c431c2bec6d54e2051b4abdf4176
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Salje, Jeanne
8f8b6016392e0acc57c37aeb1ff0ef7c
300
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2020-07-22T11:25:56Z
2020-07-22T11:25:56Z
2020-07-03
Nat Commun. 2020;11(1):3363. Published 2020 Jul 3. doi:10.1038/s41467-020-17094-8.
32620750
10.1038/s41467-020-17094-8
http://hdl.handle.net/10033/622355
2041-1723
Nature communications
Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium that causes the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning to study the transcriptional architecture of Ot, we find evidence for wide-spread post-transcriptional antisense regulation. Comparing the host response to two clinical isolates, we identify distinct immune response networks for each strain, leading to predictions of relative virulence that are validated in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
en
Nature Publishing Group
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen.
Article
11
1
3363
Nature communications
England
2020-07-22T11:25:58Z
THUMBNAIL
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Mika-Gospodorz et al.pdf
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Open Access publication
application/pdf
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https://repository.helmholtz-hzi.de/bitstream/10033/622355/1/Mika-Gospodorz%20et%20al.pdf
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MD5
1
true
10033/622355
oai:repository.helmholtz-hzi.de:10033/622355
2020-07-23 01:24:36.669
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6223682020-07-30T02:31:26Zcom_10033_620968col_10033_621182
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2020-07-29T08:59:21Z
2020-07-29T08:59:21Z
2020-06-02
mSystems. 2020;5(3):e00422-20. Published 2020 Jun 2. doi:10.1128/mSystems.00422-20.
2379-5077
32487744
10.1128/mSystems.00422-20
http://hdl.handle.net/10033/622368
mSystems
Small RNAs (sRNAs) have been discovered in every bacterium examined and have been shown to play important roles in the regulation of a diverse range of behaviors, from metabolism to infection. However, despite a wide range of available techniques for discovering and validating sRNA regulatory interactions, only a minority of these molecules have been well characterized. In part, this is due to the nature of posttranscriptional regulation: the activity of an sRNA depends on the state of the transcriptome as a whole, so characterization is best carried out under the conditions in which it is naturally active. In this issue of mSystems, Arrieta-Ortiz and colleagues (M. L. Arrieta-Ortiz, C. Hafemeister, B. Shuster, N. S. Baliga, et al., mSystems 5:e00057-20, 2020, https://doi.org/10.1128/mSystems.00057-20) present a network inference approach based on estimating sRNA activity across transcriptomic compendia. This shows promise not only for identifying new sRNA regulatory interactions but also for pinpointing the conditions in which these interactions occur, providing a new avenue toward functional characterization of sRNAs.
en
ASM
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
ncRNA
network inference
sRNA
Plugging Small RNAs into the Network.
Article
5
3
mSystems
United States
2020-07-29T08:59:22Z
THUMBNAIL
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10033/622368
oai:repository.helmholtz-hzi.de:10033/622368
2020-07-30 02:31:26.457
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6223742020-07-31T01:24:42Zcom_10033_620968col_10033_621182
Cain, Amy K
adf16e6ff6ffcec6ab2733b61bc2095e
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Goodman, Andrew L
4f956cf05c13877c408d0fe919f30e9a
300
Paulsen, Ian T
5278d4cf81f429f1bc65c17ff31ea0ca
300
Parkhill, Julian
2725d4556af2a8c6288bb04de62173dd
500
van Opijnen, Tim
d9df3d7613f1c0f19f24e1156fcee751
300
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2020-07-30T09:41:24Z
2020-07-30T09:41:24Z
2020-06-12
Nat Rev Genet. 2020;1-15. doi:10.1038/s41576-020-0244-x.
32533119
10.1038/s41576-020-0244-x
http://hdl.handle.net/10033/622374
1471-0064
Nature reviews. Genetics
PMC7291929
It has been 10 years since the introduction of modern transposon-insertion sequencing (TIS) methods, which combine genome-wide transposon mutagenesis with high-throughput sequencing to estimate the fitness contribution or essentiality of each genetic component in a bacterial genome. Four TIS variations were published in 2009: transposon sequencing (Tn-Seq), transposon-directed insertion site sequencing (TraDIS), insertion sequencing (INSeq) and high-throughput insertion tracking by deep sequencing (HITS). TIS has since become an important tool for molecular microbiologists, being one of the few genome-wide techniques that directly links phenotype to genotype and ultimately can assign gene function. In this Review, we discuss the recent applications of TIS to answer overarching biological questions. We explore emerging and multidisciplinary methods that build on TIS, with an eye towards future applications.
en
Springer Nature
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291929/
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
A decade of advances in transposon-insertion sequencing.
Review
Other
Nature reviews. Genetics
United States
England
2020-07-30T09:41:25Z
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Cain et al.pdf
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10033/622374
oai:repository.helmholtz-hzi.de:10033/622374
2020-07-31 01:24:42.568
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6225092020-10-14T01:39:04Zcom_10033_620968col_10033_621182col_10033_620969
Chihara, Kotaro
8a3ef485103de631d1a9cfec8166b412
500
Bischler, Thorsten
2381b711c4d1952c40de28faa6797621
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Monzon, Vivian A
b72365cc85dcd562d0993dc6ab879239
500
Noda, Naohiro
ac4afbf6e6138ef44020ac7ad02ce528
500
Vogel, Jörg
2df2814aef3e5077f64f75240fcbdf6c
600
http://orcid.org/0000-0003-2220-1404
Tsuneda, Satoshi
32022121d5417119c30820f5e20d5335
500
2020-10-12T15:14:17Z
2020-10-12T15:14:17Z
2019-12-03
2379-5077
31796567
10.1128/mSystems.00590-19
http://hdl.handle.net/10033/622509
mSystems
Bacterial small noncoding RNAs (sRNAs) play posttranscriptional regulatory roles in cellular responses to changing environmental cues and in adaptation to harsh conditions. Generally, the RNA-binding protein Hfq helps sRNAs associate with target mRNAs to modulate their translation and to modify global RNA pools depending on physiological state. Here, a combination of in vivo UV cross-linking immunoprecipitation followed by high-throughput sequencing (CLIP-seq) and total RNA-seq showed that Hfq interacts with different regions of the Pseudomonas aeruginosa transcriptome under planktonic versus biofilm conditions. In the present approach, P. aeruginosa Hfq preferentially interacted with repeats of the AAN triplet motif at mRNA 5' untranslated regions (UTRs) and sRNAs and U-rich sequences at rho-independent terminators. Further transcriptome analysis suggested that the association of sRNAs with Hfq is primarily a function of their expression levels, strongly supporting the notion that the pool of Hfq-associated RNAs is equilibrated by RNA concentration-driven cycling on and off Hfq. Overall, our combinatorial CLIP-seq and total RNA-seq approach highlights conditional sRNA associations with Hfq as a novel aspect of posttranscriptional regulation in P. aeruginosaIMPORTANCE The Gram-negative bacterium P. aeruginosa is ubiquitously distributed in diverse environments and can cause severe biofilm-related infections in at-risk individuals. Although the presence of a large number of putative sRNAs and widely conserved RNA chaperones in this bacterium implies the importance of posttranscriptional regulatory networks for environmental fluctuations, limited information is available regarding the global role of RNA chaperones such as Hfq in the P. aeruginosa transcriptome, especially under different environmental conditions. Here, we characterize Hfq-dependent differences in gene expression and biological processes in two physiological states: the planktonic and biofilm forms. A combinatorial comparative CLIP-seq and total RNA-seq approach uncovered condition-dependent association of RNAs with Hfq in vivo and expands the potential direct regulatory targets of Hfq in the P. aeruginosa transcriptome.
en
CLIP-seq
Hfq
Pseudomonas aeruginosa
biofilms
noncoding RNA
Conditional Hfq Association with Small Noncoding RNAs in Pseudomonas aeruginosa Revealed through Comparative UV Cross-Linking Immunoprecipitation Followed by High-Throughput Sequencing.
Article
4
6
mSystems
United States
2020-10-13T07:52:53Z
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oai:repository.helmholtz-hzi.de:10033/622509
2020-10-14 01:39:04.666
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6226712021-02-02T14:30:01Zcom_10033_620968col_10033_621182col_10033_620969
Michaux, Charlotte
e7be497b26914b746268df3d95d5dbb2
500
Hansen, Elisabeth E
3be71d2b116cc91df7dc891aaca57af6
300
Jenniches, Laura
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300
Gerovac, Milan
8a504e2a5faf8d1158813aae8fa2b785
500
Barquist, Lars
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500
Vogel, Jörg
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600
http://orcid.org/0000-0003-2220-1404
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-01-11T14:34:31Z
2021-01-11T14:34:31Z
2020-11-25
33324581
10.3389/fcimb.2020.600325
http://hdl.handle.net/10033/622671
2235-2988
Frontiers in cellular and infection microbiology
Enterococcus faecalis and faecium are two major representative clinical strains of the Enterococcus genus and are sadly notorious to be part of the top agents responsible for nosocomial infections. Despite their critical implication in worldwide public healthcare, essential and available resources such as deep transcriptome annotations remain poor, which also limits our understanding of post-transcriptional control small regulatory RNA (sRNA) functions in these bacteria. Here, using the dRNA-seq technique in combination with ANNOgesic analysis, we successfully mapped and annotated transcription start sites (TSS) of both E. faecalis V583 and E. faecium AUS0004 at single nucleotide resolution. Analyzing bacteria in late exponential phase, we capture ~40% (E. faecalis) and 43% (E. faecium) of the annotated protein-coding genes, determine 5' and 3' UTR (untranslated region) length, and detect instances of leaderless mRNAs. The transcriptome maps revealed sRNA candidates in both bacteria, some found in previous studies and new ones. Expression of candidate sRNAs is being confirmed under biologically relevant environmental conditions. This comprehensive global TSS mapping atlas provides a valuable resource for RNA biology and gene expression analysis in the Enterococci. It can be accessed online at www.helmholtz-hiri.de/en/datasets/enterococcus through an instance of the genomic viewer JBrowse.
en
Frontiers
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Gram-positive bacteria
RNA-seq
post-transcriptional regulation
sRNA atlas
transcription start sites
Single-Nucleotide RNA Maps for the Two Major Nosocomial Pathogens Enterococcus faecalis and Enterococcus faecium
Article
10
600325
Frontiers in cellular and infection microbiology
Switzerland
2021-01-11T14:34:32Z
THUMBNAIL
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oai:repository.helmholtz-hzi.de:10033/622671
2021-02-02 14:30:01.823
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6228462021-04-28T01:38:13Zcom_10033_620968col_10033_621182col_10033_621391
Ryan, Daniel
efa5f05105a82e182e292e0746bede12
500
Jenniches, Laura
f31f6016c2ce15accc4a926212cc3b96
500
Reichardt, Sarah
b1f819d36293f3b49a9ad44617241e8c
300
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Westermann, Alexander J
afd7dc94c1dc4b1cefd28cc18f09916e
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-04-27T12:31:54Z
2021-04-27T12:31:54Z
2020-07-16
Nat Commun. 2020 Jul 16;11(1):3557. doi: 10.1038/s41467-020-17348-5.
32678091
10.1038/s41467-020-17348-5
http://hdl.handle.net/10033/622846
2041-1723
Nature communications
Bacteria of the genus Bacteroides are common members of the human intestinal microbiota and important degraders of polysaccharides in the gut. Among them, the species Bacteroides thetaiotaomicron has emerged as the model organism for functional microbiota research. Here, we use differential RNA sequencing (dRNA-seq) to generate a single-nucleotide resolution transcriptome map of B. thetaiotaomicron grown under defined laboratory conditions. An online browser, called 'Theta-Base' ( www.helmholtz-hiri.de/en/datasets/bacteroides ), is launched to interrogate the obtained gene expression data and annotations of ~4500 transcription start sites, untranslated regions, operon structures, and 269 noncoding RNA elements. Among the latter is GibS, a conserved, 145 nt-long small RNA that is highly expressed in the presence of N-acetyl-D-glucosamine as sole carbon source. We use computational predictions and experimental data to determine the secondary structure of GibS and identify its target genes. Our results indicate that sensing of N-acetyl-D-glucosamine induces GibS expression, which in turn modifies the transcript levels of metabolic enzymes.
en
NPG
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
A high-resolution transcriptome map identifies small RNA regulation of metabolism in the gut microbe Bacteroides thetaiotaomicron.
Article
11
1
3557
Nature communications
England
2021-04-27T12:31:55Z
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10033/622846
oai:repository.helmholtz-hzi.de:10033/622846
2021-04-28 01:38:13.555
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6228472021-04-28T01:38:20Zcom_10033_620968col_10033_621182col_10033_620969
Bauriedl, Saskia
144e0f240d99fdab29ea030d0abf512a
500
Gerovac, Milan
8a504e2a5faf8d1158813aae8fa2b785
500
Heidrich, Nadja
a9329c5988f8f2f344d34a88ae97fb29
500
Bischler, Thorsten
2381b711c4d1952c40de28faa6797621
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Vogel, Jörg
2df2814aef3e5077f64f75240fcbdf6c
600
http://orcid.org/0000-0003-2220-1404
Schoen, Christoph
44ef615d74adcab5264f7b3efb26f59c
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-04-27T13:57:22Z
2021-04-27T13:57:22Z
2020-06-04
Nat Commun. 2020 Jun 4;11(1):2823. doi: 10.1038/s41467-020-16650-6.
32499480
10.1038/s41467-020-16650-6
http://hdl.handle.net/10033/622847
2041-1723
Nature communications
FinO-domain proteins are a widespread family of bacterial RNA-binding proteins with regulatory functions. Their target spectrum ranges from a single RNA pair, in the case of plasmid-encoded FinO, to global RNA regulons, as with enterobacterial ProQ. To assess whether the FinO domain itself is intrinsically selective or promiscuous, we determine in vivo targets of Neisseria meningitidis, which consists of solely a FinO domain. UV-CLIP-seq identifies associations with 16 small non-coding sRNAs and 166 mRNAs. Meningococcal ProQ predominantly binds to highly structured regions and generally acts to stabilize its RNA targets. Loss of ProQ alters transcript levels of >250 genes, demonstrating that this minimal ProQ protein impacts gene expression globally. Phenotypic analyses indicate that ProQ promotes oxidative stress resistance and DNA damage repair. We conclude that FinO domain proteins recognize some abundant type of RNA shape and evolve RNA binding selectivity through acquisition of additional regions that constrain target recognition.
en
Nature Research
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
The minimal meningococcal ProQ protein has an intrinsic capacity for structure-based global RNA recognition.
Article
11
1
2823
Nature communications
England
2021-04-27T13:57:22Z
THUMBNAIL
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Bauriedl et al.pdf
Open Access publication
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10033/622847
oai:repository.helmholtz-hzi.de:10033/622847
2021-04-28 01:38:20.964
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6228982021-06-09T01:46:46Zcom_10033_620968col_10033_621182
Chihara, Kotaro
8a3ef485103de631d1a9cfec8166b412
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Takasugi, Kenichi
86a44fef304bfcc0c9b80cec12ad9dea
300
Noda, Naohiro
ac4afbf6e6138ef44020ac7ad02ce528
500
Tsuneda, Satoshi
32022121d5417119c30820f5e20d5335
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-06-08T09:41:30Z
2021-06-08T09:41:30Z
2021-04-27
RNA Biol. 2021 Apr 27:1-16. doi: 10.1080/15476286.2021.1917184. Epub ahead of print.
33866926
10.1080/15476286.2021.1917184
http://hdl.handle.net/10033/622898
1555-8584
RNA biology
Pseudomonas aeruginosa harbours two redundant RNA-binding proteins RsmA/RsmN (RsmA/N), which play a critical role in balancing acute and chronic infections. However, in vivo binding sites on target transcripts and the overall impact on the physiology remains unclear. In this study, we applied in vivo UV crosslinking immunoprecipitation followed by RNA-sequencing (UV CLIP-seq) to detect RsmA/N-binding sites at single-nucleotide resolution and mapped more than 500 binding sites to approximately 400 genes directly bound by RsmA/N in P. aeruginosa. This also verified the ANGGA sequence in apical loops skewed towards 5'UTRs as a consensus motif for RsmA/N binding. Genetic analysis combined with CLIP-seq results suggested previously unrecognized RsmA/N targets involved in LPS modification. Moreover, the RsmA/N-titrating RNAs RsmY/RsmZ may be positively regulated by the RsmA/N-mediated translational repression of their upstream regulators, thus providing a possible mechanistic explanation for homoeostasis of the Rsm system. Thus, our study provides a detailed view of RsmA/N-RNA interactions and a resource for further investigation of the pleiotropic effects of RsmA/N on gene expression in P. aeruginosa.
en
Taylor & Francis
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
CLIP-seq
Pseudomonas aeruginosa
RsmA
RsmN
post-transcriptional regulation
Global identification of RsmA/N binding sites in by UV CLIP-seq.
Article
1
16
RNA biology
United States
2021-06-08T09:41:30Z
THUMBNAIL
Chihara et al.pdf.jpg
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Chihara et al.pdf
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oai:repository.helmholtz-hzi.de:10033/622898
2021-06-09 01:46:46.139
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6228992021-06-09T01:46:53Zcom_10033_620968col_10033_621182col_10033_620969
Popella, Linda
88336a3669135689e28fabe0dc673968
300
Jung, Jakob
59bd13b8717fa8b72e4cd498d3718862
300
Popova, Kristina
de2c72e844d53c595758cc58b5d0a659
300
Ðurica-Mitić, Svetlana
80253dd41c400a0af7744f669f744380
300
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Vogel, Jörg
1a02c431c2bec6d54e2051b4abdf4176
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-06-08T11:39:42Z
2021-06-08T11:39:42Z
33849070
10.1093/nar/gkab242
http://hdl.handle.net/10033/622899
1362-4962
Nucleic acids research
Antisense peptide nucleic acids (PNAs) inhibiting mRNAs of essential genes provide a straight-forward way to repurpose our knowledge of bacterial regulatory RNAs for development of programmable species-specific antibiotics. While there is ample proof of PNA efficacy, their target selectivity and impact on bacterial physiology are poorly understood. Moreover, while antibacterial PNAs are typically designed to block mRNA translation, effects on target mRNA levels are not well-investigated. Here, we pioneer the use of global RNA-seq analysis to decipher PNA activity in a transcriptome-wide manner. We find that PNA-based antisense oligomer conjugates robustly decrease mRNA levels of the widely-used target gene, acpP, in Salmonella enterica, with limited off-target effects. Systematic analysis of several different PNA-carrier peptides attached not only shows different bactericidal efficiency, but also activation of stress pathways. In particular, KFF-, RXR- and Tat-PNA conjugates especially induce the PhoP/Q response, whereas the latter two additionally trigger several distinct pathways. We show that constitutive activation of the PhoP/Q response can lead to Tat-PNA resistance, illustrating the utility of RNA-seq for understanding PNA antibacterial activity. In sum, our study establishes an experimental framework for the design and assessment of PNA antimicrobials in the long-term quest to use these for precision editing of microbiota.
en
Oxford University Press
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Global RNA profiles show target selectivity and physiological effects of peptide-delivered antisense antibiotics.
Article
49
8
4705
4724
Nucleic acids research
England
2021-06-08T11:39:42Z
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10033/622899
oai:repository.helmholtz-hzi.de:10033/622899
2021-06-09 01:46:53.925
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6229202021-07-02T01:42:38Zcom_10033_620968col_10033_621182
Abd El Ghany, Moataz
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Barquist, Lars
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Clare, Simon
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Brandt, Cordelia
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Mayho, Matthew
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Joffre, Enrique
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Sjöling, Åsa
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Turner, A Keith
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Klena, John D
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Kingsley, Robert A
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Hill-Cawthorne, Grant A
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Dougan, Gordon
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Pickard, Derek
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500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-07-01T14:44:59Z
2021-07-01T14:44:59Z
Microb Genom. 2021 Jun;7(6). doi: 10.1099/mgen.0.000554.
34110281
10.1099/mgen.0.000554
http://hdl.handle.net/10033/622920
2057-5858
Microbial genomics
Enterotoxigenic Escherichia coli (ETEC) expressing the colonization pili CFA/I are common causes of diarrhoeal infections in humans. Here, we use a combination of transposon mutagenesis and transcriptomic analysis to identify genes and pathways that contribute to ETEC persistence in water environments and colonization of a mammalian host. ETEC persisting in water exhibit a distinct RNA expression profile from those growing in richer media. Multiple pathways were identified that contribute to water survival, including lipopolysaccharide biosynthesis and stress response regulons. The analysis also indicated that ETEC growing in vivo in mice encounter a bottleneck driving down the diversity of colonizing ETEC populations.
en
Microbiology Society
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
CFA/I
ETEC
H10407
RNAseq
TraDIS
water survival and colonization
Functional analysis of colonization factor antigen I positive enterotoxigenic identifies genes implicated in survival in water and host colonization.
Article
7
6
Microbial genomics
England
2021-07-01T14:45:00Z
THUMBNAIL
Abd El Ghany et al.pdf.jpg
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Abd El Ghany et al.pdf
Abd El Ghany et al.pdf
Open Access publication
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https://repository.helmholtz-hzi.de/bitstream/10033/622920/1/Abd%20El%20Ghany%20et%20al.pdf
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10033/622920
oai:repository.helmholtz-hzi.de:10033/622920
2021-07-02 01:42:38.772
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6229332021-07-13T01:41:54Zcom_10033_620968col_10033_621182
Hayward, Regan J
b24f72b83781cd492049aa3151ede3ca
300
Humphrys, Michael S
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300
Huston, Wilhelmina M
58a2f6cd074bd5ff2fcc578e905ef211
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Myers, Garry S A
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300
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-07-12T09:25:51Z
2021-07-12T09:25:51Z
2021-05-17
Sci Rep. 2021 May 17;11(1):10399. doi: 10.1038/s41598-021-89921-x.
34001998
10.1038/s41598-021-89921-x
http://hdl.handle.net/10033/622933
2045-2322
Scientific reports
Dual RNA-seq experiments examining viral and bacterial pathogens are increasing, but vary considerably in their experimental designs, such as infection rates and RNA depletion methods. Here, we have applied dual RNA-seq to Chlamydia trachomatis infected epithelial cells to examine transcriptomic responses from both organisms. We compared two time points post infection (1 and 24 h), three multiplicity of infection (MOI) ratios (0.1, 1 and 10) and two RNA depletion methods (rRNA and polyA). Capture of bacterial-specific RNA were greatest when combining rRNA and polyA depletion, and when using a higher MOI. However, under these conditions, host RNA capture was negatively impacted. Although it is tempting to use high infection rates, the implications on host cell survival, the potential reduced length of infection cycles and real world applicability should be considered. This data highlights the delicate nature of balancing host-pathogen RNA capture and will assist future transcriptomic-based studies to achieve more specific and relevant infection-related biological insights.
en
Nature Research
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Dual RNA-seq analysis of in vitro infection multiplicity and RNA depletion methods in Chlamydia-infected epithelial cells.
Article
11
1
10399
Scientific reports
England
2021-07-12T09:25:52Z
THUMBNAIL
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Hayward et al.pdf.txt
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Hayward et al.pdf
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Open Access publication
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10033/622933
oai:repository.helmholtz-hzi.de:10033/622933
2021-07-13 01:41:54.934
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6229792021-08-06T01:53:30Zcom_10033_620968col_10033_621182col_10033_620969
Fuchs, Manuela
6615e8fd6af4d61a964ef268a2306fa9
300
Lamm-Schmidt, Vanessa
4d1ce1e2ee60b28fdd7dfe2c50e98003
300
Sulzer, Johannes
7e6cf6d9269929b76b85b0c565c956e0
300
Ponath, Falk
1106f0ac6400c6a771d3daced0e0eb09
500
Jenniches, Laura
f31f6016c2ce15accc4a926212cc3b96
500
Kirk, Joseph A
e26632d955ef022720008dbe8f3d07c1
300
Fagan, Robert P
38b1e1dd8acb09b93b6a5f0592833e40
300
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Vogel, Jörg
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600
http://orcid.org/0000-0003-2220-1404
Faber, Franziska
48eb40a406cecad051d613887a1e9317
300
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-08-05T12:12:51Z
2021-08-05T12:12:51Z
2021-06-15
Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):e2103579118. doi: 10.1073/pnas.2103579118.
34131082
10.1073/pnas.2103579118
http://hdl.handle.net/10033/622979
1091-6490
Proceedings of the National Academy of Sciences of the United States of America
The gram-positive human pathogen Clostridioides difficile has emerged as the leading cause of antibiotic-associated diarrhea. However, little is known about the bacterium's transcriptome architecture and mechanisms of posttranscriptional control. Here, we have applied transcription start site and termination mapping to generate a single-nucleotide-resolution RNA map of C. difficile 5' and 3' untranslated regions, operon structures, and noncoding regulators, including 42 sRNAs. Our results indicate functionality of many conserved riboswitches and predict cis-regulatory RNA elements upstream of multidrug resistance (MDR)-type ATP-binding cassette (ABC) transporters and transcriptional regulators. Despite growing evidence for a role of Hfq in RNA-based gene regulation in C. difficile, the functions of Hfq-based posttranscriptional regulatory networks in gram-positive pathogens remain controversial. Using Hfq immunoprecipitation followed by sequencing of bound RNA species (RIP-seq), we identify a large cohort of transcripts bound by Hfq and show that absence of Hfq affects transcript stabilities and steady-state levels. We demonstrate sRNA expression during intestinal colonization by C. difficile and identify infection-related signals impacting its expression. As a proof of concept, we show that the utilization of the abundant intestinal metabolite ethanolamine is regulated by the Hfq-dependent sRNA CDIF630nc_085. Overall, our study lays the foundation for understanding clostridial riboregulation with implications for the infection process and provides evidence for a global role of Hfq in posttranscriptional regulation in a gram-positive bacterium.
en
National Academy of Sciences
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
C. difficile
Hfq
differential RNA-seq
small RNA
transcript termination site
An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium.
Article
118
25
Proceedings of the National Academy of Sciences of the United States of America
United Kingdom
United States
2021-08-05T12:12:52Z
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oai:repository.helmholtz-hzi.de:10033/6230092021-09-02T02:42:17Zcom_10033_620968col_10033_621182col_10033_620969
Ponath, Falk
1106f0ac6400c6a771d3daced0e0eb09
500
Tawk, Caroline
5fc0e6a482b0fab4496f2da846dd383a
500
Zhu, Yan
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300
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Faber, Franziska
48eb40a406cecad051d613887a1e9317
500
Vogel, Jörg
1a02c431c2bec6d54e2051b4abdf4176
500
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2021-09-01T07:45:39Z
2021-09-01T07:45:39Z
2021-07-08
34239075
10.1038/s41564-021-00927-7
http://hdl.handle.net/10033/623009
2058-5276
Nature microbiology
Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.
en
Nature Research
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.
Article
6
8
1007
1020
Nature microbiology
England
THUMBNAIL
2022-01-08
Ponath et al.pdf.jpg
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2022-01-08
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oai:repository.helmholtz-hzi.de:10033/6231532022-01-28T02:17:22Zcom_10033_620968col_10033_621182col_10033_621391
Prezza, Gianluca
8971fcb2d6679344b255744d54579bae
500
Ryan, Daniel
efa5f05105a82e182e292e0746bede12
500
Mädler, Gohar
0b792b469cc453e3d18adcfb81baaff5
300
Reichardt, Sarah
b1f819d36293f3b49a9ad44617241e8c
500
Barquist, Lars
54c1e18acbb850f2e20e176252ce903a
500
Westermann, Alexander J
afd7dc94c1dc4b1cefd28cc18f09916e
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
2022-01-27T09:56:06Z
2022-01-27T09:56:06Z
2021-08-28
Mol Microbiol. 2022 Jan;117(1):67-85. doi: 10.1111/mmi.14793. Epub 2021 Aug 28.
34379855
10.1111/mmi.14793
http://hdl.handle.net/10033/623153
1365-2958
Molecular microbiology
Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA-binding proteins and predict a Bacteroides cold-shock protein homolog to have an RNA-related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members.
en
Wiley & Sons Ltd.
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
6S RNA
BT_1884
GibS
RNA-binding proteins
cold-shock protein
secondary structure
Comparative genomics provides structural and functional insights into Bacteroides RNA biology.
Article
117
1
67
85
Molecular microbiology
England
2022-01-27T09:56:06Z
THUMBNAIL
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Prezza et al.pdf.txt
Prezza et al.pdf.txt
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Prezza et al.pdf
Prezza et al.pdf
Open Access article
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10033/623153
oai:repository.helmholtz-hzi.de:10033/623153
2022-01-28 02:17:22.728
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6232332022-06-17T02:02:02Zcom_10033_620968col_10033_621182
Elliott, Alysha G
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Huang, Johnny X
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Neve, Søren
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Zuegg, Johannes
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Edwards, Ingrid A
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Cain, Amy K
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Boinett, Christine J
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Barquist, Lars
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Lundberg, Carina Vingsbo
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Steen, Jason
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Butler, Mark S
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Mobli, Mehdi
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Porter, Kaela M
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Blaskovich, Mark A T
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Lociuro, Sergio
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Strandh, Magnus
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Cooper, Matthew A
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2022-06-16T13:11:09Z
2022-06-16T13:11:09Z
2020-06-23
2020-02-12
32576824
10.1038/s41467-020-16950-x
http://hdl.handle.net/10033/623233
2041-1723
Nature communications
Peptide antibiotics are an abundant and synthetically tractable source of molecular diversity,
but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has
limited their clinical development. Here we report structure-guided optimization of an
amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina.
The peptide induces bacterial membrane permeability and ATP release, with serial passaging
resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to
AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and
extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical
isolates. The antibiotic induces a 3–4 log reduction in bacterial burden in mouse models of
peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the ‘no observable adverse effect level’
(NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the
infection models
en
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria.
Article
11
1
3184
Nature communications
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
England
2022-06-16T13:11:10Z
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10033/623233
oai:repository.helmholtz-hzi.de:10033/623233
2022-06-17 02:02:02.422
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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