Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305878
Title:
Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.
Authors:
Tielen, Petra; Rosin, Nathalie; Meyer, Ann-Kathrin; Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar ( 0000-0002-5655-1181 ) ; Klein, Johannes; Narten, Maike; Pommerenke, Claudia ( 0000-0002-9448-416X ) ; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter
Abstract:
Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections.
Affiliation:
Institute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany. p.tielen@tu-bs.de
Citation:
Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions. 2013, 8 (8):e71845 PLoS ONE
Journal:
PloS one
Issue Date:
2013
URI:
http://hdl.handle.net/10033/305878
DOI:
10.1371/journal.pone.0071845
PubMed ID:
23967252
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of RG Cellular Proteome Research (CPRO)

Full metadata record

DC FieldValue Language
dc.contributor.authorTielen, Petraen
dc.contributor.authorRosin, Nathalieen
dc.contributor.authorMeyer, Ann-Kathrinen
dc.contributor.authorDohnt, Katrinen
dc.contributor.authorHaddad, Isamen
dc.contributor.authorJänsch, Lotharen
dc.contributor.authorKlein, Johannesen
dc.contributor.authorNarten, Maikeen
dc.contributor.authorPommerenke, Claudiaen
dc.contributor.authorScheer, Mauriceen
dc.contributor.authorSchobert, Maxen
dc.contributor.authorSchomburg, Dietmaren
dc.contributor.authorThielen, Bernharden
dc.contributor.authorJahn, Dieteren
dc.date.accessioned2013-11-28T11:37:37Zen
dc.date.available2013-11-28T11:37:37Zen
dc.date.issued2013en
dc.identifier.citationRegulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions. 2013, 8 (8):e71845 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid23967252en
dc.identifier.doi10.1371/journal.pone.0071845en
dc.identifier.urihttp://hdl.handle.net/10033/305878en
dc.description.abstractBiofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections.en
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen
dc.titleRegulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.en
dc.typeArticleen
dc.contributor.departmentInstitute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany. p.tielen@tu-bs.deen
dc.identifier.journalPloS oneen

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