title: Regulation of type VI secretion system during Burkholderia pseudomallei infection.
abstract: Type III and type VI secretion systems (T3SSs and T6SSs, respectively) are critical virulence determinants in several Gram-negative pathogens. In Burkholderia pseudomallei, the T3SS-3 and T6SS-1 clusters have been implicated in bacterial virulence in mammalian hosts. We recently discovered a regulatory cascade that coordinately controls the expression of T3SS-3 and T6SS-1. BsaN is a central regulator located within T3SS-3 for the expression of T3SS-3 effectors and regulators for T6SS-1 such as VirA-VirG (VirAG) and BprC. Whereas T6SS-1 gene expression was completely dependent on BprC when bacteria were grown in medium, the expression inside host cells was dependent on the two-component sensor-regulator VirAG, with the exception of the tssAB operon, which was dependent primarily on BprC. VirAG and BprC initiate different transcriptional start sites within T6SS-1, and VirAG is able to activate the hcp1 promoter directly. We also provided novel evidence that virAG, bprC, and tssAB are critical for T6SS-1 function in macrophages. Furthermore, virAG and bprC regulator mutants were avirulent in mice, demonstrating the absolute dependence of T6SS-1 expression on these regulators in vivo.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Yahua
authors.initials: Y
authors.lastname: Chen
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Wong
authors.forename: Guang Wen
authors.initials: GW
authors.lastname: Sun
authors.forename: Yichun
authors.initials: Y
authors.lastname: Liu
authors.forename: Gek-Yen Gladys
authors.initials: GY
authors.lastname: Tan
authors.forename: Yunn-Hwen
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000818:Animals; D019121:Burkholderia Infections / Q000382:microbiology / Q000473:pathology*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D046911:Macromolecular Substances / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012376:Rodent Diseases / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D015534:Trans-Activators; D037521:Virulence Factors