title: Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.
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.
authors: Institute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany. p.tielen@tu-bs.de
authors: Petra
authors: P
authors: Tielen
authors: Nathalie
authors: N
authors: Rosin
authors: Ann-Kathrin
authors: AK
authors: Meyer
authors: Katrin
authors: K
authors: Dohnt
authors: Isam
authors: I
authors: Haddad
authors: Lothar
authors: L
authors: Jänsch
authors: Johannes
authors: J
authors: Klein
authors: Maike
authors: M
authors: Narten
authors: Claudia
authors: C
authors: Pommerenke
authors: Maurice
authors: M
authors: Scheer
authors: Max
authors: M
authors: Schobert
authors: Dietmar
authors: D
authors: Schomburg
authors: Bernhard
authors: B
authors: Thielen
authors: Dieter
authors: D
authors: Jahn
mesh_terms: D000222:Adaptation, Physiological; D000464:Alginates / Q000378:metabolism; D024322:Amino Acids, Aromatic / Q000378:metabolism; D018441:Biofilms; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D020723:Glucuronic Acid / Q000378:metabolism; D006603:Hexuronic Acids / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D020543:Proteome; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing; D013312:Stress, Physiological; D014552:Urinary Tract Infections / Q000382:microbiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000464:Alginates; D024322:Amino Acids, Aromatic; D006603:Hexuronic Acids; D020543:Proteome; D037521:Virulence Factors; D020723:Glucuronic Acid; D007501:Iron
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