title: Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways.
abstract: Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a range of factors including type IV pili (tfp), the type III secretion system (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage to mammalian cells. We describe a novel gene (fimL) that is required for tfp biogenesis and function, for TTS and for normal biofilm development in P. aeruginosa. The predicted product of fimL is homologous to the N-terminal domain of ChpA, except that its putative histidine and threonine phosphotransfer sites have been replaced with glutamine. fimL mutants resemble vfr mutants in many aspects including increased autolysis, reduced levels of surface-assembled tfp and diminished production of type III secreted effectors. Expression of vfr in trans can complement fimL mutants. vfr transcription and production is reduced in fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced. These results suggest that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that Vfr and FimL are components of intersecting pathways that control twitching motility, TTSS and autolysis in P. aeruginosa.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Whitchurch
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: James C
authors.initials: JC
authors.lastname: Comolli
authors.forename: Thania
authors.initials: T
authors.lastname: Jakobsen
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sargent
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Bertrand
authors.forename: Joyce
authors.initials: J
authors.lastname: West
authors.forename: Mikkel
authors.initials: M
authors.lastname: Klausen
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Waite
authors.forename: Pil Jung
authors.initials: PJ
authors.lastname: Kang
authors.forename: Tim
authors.initials: T
authors.lastname: Tolker-Nielsen
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.forename: Joanne N
authors.initials: JN
authors.lastname: Engel
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014157:Transcription Factors / Q000378:metabolism*; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; D014157:Transcription Factors; C091090:Vfr protein, Pseudomonas aeruginosa; D036781:Fimbriae Proteins; D000242:Cyclic AMP
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