Quorum sensing differentially regulates Pseudomonas aeruginosa type VI secretion locus I and homologous loci II and III, which are required for pathogenesis

Microbiology (Reading). 2009 Sep;155(Pt 9):2845-2855. doi: 10.1099/mic.0.029082-0. Epub 2009 Jun 4.


Pseudomonas aeruginosa harbours three type VI secretion (T6S) loci. Although HSI-I has been partially studied, limited knowledge is available on the homologous loci HSI-II and HSI-III. We show that quorum sensing (QS) differentially regulates the expression of genes at all three loci. HSI-I-associated gene expression is suppressed by both the homoserine lactone transcription factor LasR and the 4-hydroxy-2-alkylquinoline (HAQ) transcriptional regulator MvfR. Conversely, both HSI-II and HSI-III loci are positively controlled by LasR and MvfR. PqsE, a key component of the MvfR regulon, is required for the expression of part of HSI-III but not HSI-II, and previously identified inhibitors of HAQ biosynthesis significantly downregulate HSI-II and -III gene expression. Animal and plant infection studies reveal that both HSI-II and -III play important roles in pathogenesis. Furthermore, analysis of a double DeltaHSI-II : : III mutant suggests that these loci functionally compensate for one another in virulence. This study illustrates the contribution of the QS systems to T6S gene regulation and reveals the importance of HSI-II and -III in mediating P. aeruginosa pathogenesis. Moreover, this work provides new insights into the design and development of selective compounds that may restrict human P. aeruginosa and possibly other clinical infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Chlorobenzoates
  • DNA, Bacterial / analysis
  • DNA, Bacterial / genetics
  • Gene Expression / drug effects
  • Gene Expression Regulation, Bacterial*
  • Humans
  • Mice
  • Multigene Family*
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / metabolism*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / pathogenicity*
  • Pseudomonas aeruginosa / physiology
  • Quorum Sensing*
  • Sequence Analysis, DNA
  • Trans-Activators / metabolism
  • Virulence
  • ortho-Aminobenzoates / pharmacology


  • 2-amino-6-chlorobenzoic acid
  • Bacterial Proteins
  • Chlorobenzoates
  • DNA, Bacterial
  • LasR protein, Pseudomonas aeruginosa
  • Trans-Activators
  • ortho-Aminobenzoates
  • 2-amino-4-chlorobenzoic acid

Associated data

  • GEO/GSE17147