title: High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites.
abstract: The Pseudomonas aeruginosa type III secretion system (T3SS) is known to be a very important virulence factor in acute human infections, but it is less important in maintaining chronic infections in which T3SS genes are downregulated. In vitro, the activation of T3SS expression involves a positive activating loop that acts on the transcriptional regulator ExsA. We have observed that in vivo T3SS expression is cell density-dependent in a manner that does not need known quorum-sensing (QS) signals. In addition, stationary-phase culture supernatants added to exponential-phase growing strains can inhibit T3SS expression. The analysis of transposon insertion mutants showed that the production of such T3SS-inhibiting signals might depend on tryptophan synthase and hence tryptophan, which is the precursor of signalling molecules such as indole-3-acetic acid (IAA), kynurenine and Pseudomonas quinolone signal (PQS). Commercially available tryptophan-derived molecules were tested for their role in the regulation of T3SS expression. At millimolar concentrations, IAA, 1-naphthalacetic acid (NAA) and 3-hydroxykynurenine inhibited T3SS expression. Inactivation of the tryptophan dioxygenase-encoding kynA gene resulted in a decrease in the T3SS-inhibiting activity of supernatants. These observations suggest that tryptophan catabolites are involved in the downregulation of T3SS expression in the transition from a low- to a high-cell-density state.
authors.affiliation: Department of Microbiology and Parasitology, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, PR China.|GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Da-Kang
authors.initials: DK
authors.lastname: Shen
authors.affiliation: GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Filopon
authors.affiliation: GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Hichem
authors.initials: H
authors.lastname: Chaker
authors.affiliation: Service Spectrométrie de Masse, CERMAV-CNRS, BP53, 38041 Grenoble cedex 9, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Boullanger
authors.affiliation: GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.affiliation: GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Polack
authors.affiliation: GREPI, TIMC-IMAG, UMR5525 CNRS/Université Joseph Fourier Faculté de Médecine, Bat. J Roget, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D007210:Indoleacetic Acids / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007210:Indoleacetic Acids; D037521:Virulence Factors; C005045:3-hydroxykynurenine; D007737:Kynurenine; C030737:indoleacetic acid; D014364:Tryptophan