title: VqsM, a novel AraC-type global regulator of quorum-sensing signalling and virulence in Pseudomonas aeruginosa.
abstract: Human pathogen Pseudomonas aeruginosa uses quorum-sensing (QS) signalling systems to synchronize the production of virulence factors. There are two interrelated QS systems, las and rhl, in P. aeruginosa. In addition to this complexity, a number of transcriptional regulators were shown to have complicated interplays with las and rhl central QS components. Here, we describe a novel virulence and QS modulator (VqsM) that positively regulates the QS systems in P. aeruginosa. Mutation in vqsM resulted in much reduced production of N-acylhomoserine lactones (AHLs) and extracellular enzymes. Sequence analysis revealed that vqsM encodes a transcriptional regulator with an AraC-type helix-turn-helix DNA binding domain at the C-terminal of the peptide. Global gene expression profile analysis showed at least a total of 302 genes to be influenced, directly or indirectly, by VqsM. Among the 203 VqsM-promoted genes, 52.2% were known to be QS upregulated. Several genes encoding the key regulators implicated in QS, such as rhlR, rsaL, vqsR, mvfR, pprB and rpoS, and two AHL synthesis genes, lasI and rhlI, were suppressed in the vqsM mutant. Similar to the 'AHL-blind' phenotype of vqsR and pprB mutants, vqsM mutant did not respond to external addition of N-3-oxo-dodecanoyl-homoserine lactone signals. Moreover, overexpression of vqsR in vqsM mutant more or less restored the production of both AHL and virulence factors. The results demonstrate that VqsM, largely through modulation of vqsR expression, plays a vital role in regulation of QS signalling in P. aeruginosa.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673, Singapore.
authors.forename: Yi-Hu
authors.initials: YH
authors.lastname: Dong
authors.forename: Xi-Fen
authors.initials: XF
authors.lastname: Zhang
authors.forename: Jin-Ling
authors.initials: JL
authors.lastname: Xu
authors.forename: Ai-Tee
authors.initials: AT
authors.lastname: Tan
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051777:AraC Transcription Factor / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051777:AraC Transcription Factor; D001426:Bacterial Proteins; D037521:Virulence Factors; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase