title: Quorum sensing differentially regulates Pseudomonas aeruginosa type VI secretion locus I and homologous loci II and III, which are required for pathogenesis.
abstract: 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.
authors.affiliation: Shriners Burns Institute, Boston, MA, USA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lesic
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.|Shriners Burns Institute, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Starkey
authors.affiliation: Shriners Burns Institute, Boston, MA, USA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Shriners Burns Institute, Boston, MA, USA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hazan
authors.affiliation: Shriners Burns Institute, Boston, MA, USA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Rahme
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002723:Chlorobenzoates; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D005810:Multigene Family; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D053038:Quorum Sensing; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000378:metabolism; D014774:Virulence; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: C544935:2-amino-6-chlorobenzoic acid; D001426:Bacterial Proteins; D002723:Chlorobenzoates; D004269:DNA, Bacterial; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators; D062367:ortho-Aminobenzoates; C544934:2-amino-4-chlorobenzoic acid