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dc.contributor.authorLassek, Christian
dc.contributor.authorBurghartz, Melanie
dc.contributor.authorChaves-Moreno, Diego
dc.contributor.authorOtto, Andreas
dc.contributor.authorHentschker, Christian
dc.contributor.authorFuchs, Stephan
dc.contributor.authorBernhardt, Jörg
dc.contributor.authorJauregui, Ruy
dc.contributor.authorNeubauer, Rüdiger
dc.contributor.authorBecher, Dörte
dc.contributor.authorPieper, Dietmar H
dc.contributor.authorJahn, Martina
dc.contributor.authorJahn, Dieter
dc.contributor.authorRiedel, Katharina
dc.date.accessioned2017-11-20T14:31:37Z
dc.date.available2017-11-20T14:31:37Z
dc.date.issued2015-04
dc.identifier.citationA metaproteomics approach to elucidate host and pathogen protein expression during catheter-associated urinary tract infections (CAUTIs). 2015, 14 (4):989-1008 Mol. Cell Proteomicsen
dc.identifier.issn1535-9484
dc.identifier.pmid25673765
dc.identifier.doi10.1074/mcp.M114.043463
dc.identifier.urihttp://hdl.handle.net/10033/621180
dc.description.abstractLong-term catheterization inevitably leads to a catheter-associated bacteriuria caused by multispecies bacterial biofilms growing on and in the catheters. The overall goal of the presented study was (1) to unravel bacterial community structure and function of such a uropathogenic biofilm and (2) to elucidate the interplay between bacterial virulence and the human immune system within the urine. To this end, a metaproteomics approach combined with in vitro proteomics analyses was employed to investigate both, the pro- and eukaryotic protein inventory. Our proteome analyses demonstrated that the biofilm of the investigated catheter is dominated by three bacterial species, that is, Pseudomonas aeruginosa, Morganella morganii, and Bacteroides sp., and identified iron limitation as one of the major challenges in the bladder environment. In vitro proteome analysis of P. aeruginosa and M. morganii isolated from the biofilm revealed that these opportunistic pathogens are able to overcome iron restriction via the production of siderophores and high expression of corresponding receptors. Notably, a comparison of in vivo and in vitro protein profiles of P. aeruginosa and M. morganii also indicated that the bacteria employ different strategies to adapt to the urinary tract. Although P. aeruginosa seems to express secreted and surface-exposed proteases to escape the human innate immune system and metabolizes amino acids, M. morganii is able to take up sugars and to degrade urea. Most interestingly, a comparison of urine protein profiles of three long-term catheterized patients and three healthy control persons demonstrated the elevated level of proteins associated with neutrophils, macrophages, and the complement system in the patient's urine, which might point to a specific activation of the innate immune system in response to biofilm-associated urinary tract infections. We thus hypothesize that the often asymptomatic nature of catheter-associated urinary tract infections might be based on a fine-tuned balance between the expression of bacterial virulence factors and the human immune system.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAdaptation, Physiologicalen
dc.subject.meshBacterial Proteinsen
dc.subject.meshBiofilmsen
dc.subject.meshCatheter-Related Infectionsen
dc.subject.meshCell-Free Systemen
dc.subject.meshHost-Pathogen Interactionsen
dc.subject.meshHumansen
dc.subject.meshImmunity, Innateen
dc.subject.meshMorganella morganiien
dc.subject.meshPhenotypeen
dc.subject.meshProteomicsen
dc.subject.meshPseudomonas aeruginosaen
dc.subject.meshSpecies Specificityen
dc.subject.meshUrinary Tracten
dc.subject.meshUrinary Tract Infectionsen
dc.subject.meshUrineen
dc.titleA metaproteomics approach to elucidate host and pathogen protein expression during catheter-associated urinary tract infections (CAUTIs).en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalMolecular & cellular proteomics : MCPen
refterms.dateFOA2018-06-13T15:56:33Z
html.description.abstractLong-term catheterization inevitably leads to a catheter-associated bacteriuria caused by multispecies bacterial biofilms growing on and in the catheters. The overall goal of the presented study was (1) to unravel bacterial community structure and function of such a uropathogenic biofilm and (2) to elucidate the interplay between bacterial virulence and the human immune system within the urine. To this end, a metaproteomics approach combined with in vitro proteomics analyses was employed to investigate both, the pro- and eukaryotic protein inventory. Our proteome analyses demonstrated that the biofilm of the investigated catheter is dominated by three bacterial species, that is, Pseudomonas aeruginosa, Morganella morganii, and Bacteroides sp., and identified iron limitation as one of the major challenges in the bladder environment. In vitro proteome analysis of P. aeruginosa and M. morganii isolated from the biofilm revealed that these opportunistic pathogens are able to overcome iron restriction via the production of siderophores and high expression of corresponding receptors. Notably, a comparison of in vivo and in vitro protein profiles of P. aeruginosa and M. morganii also indicated that the bacteria employ different strategies to adapt to the urinary tract. Although P. aeruginosa seems to express secreted and surface-exposed proteases to escape the human innate immune system and metabolizes amino acids, M. morganii is able to take up sugars and to degrade urea. Most interestingly, a comparison of urine protein profiles of three long-term catheterized patients and three healthy control persons demonstrated the elevated level of proteins associated with neutrophils, macrophages, and the complement system in the patient's urine, which might point to a specific activation of the innate immune system in response to biofilm-associated urinary tract infections. We thus hypothesize that the often asymptomatic nature of catheter-associated urinary tract infections might be based on a fine-tuned balance between the expression of bacterial virulence factors and the human immune system.


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