Open AccessRegulation of Type VI Secretion System during Burkholderia pseudomallei Infection
Author(s) -
Yahua Chen,
John Chee Meng Wong,
Guozhe Sun,
Yichun Liu,
Gek-Yen Gladys Tan,
YunnHwen Gan
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.05148-11
Subject(s) - biology , type vi secretion system , virulence , effector , type three secretion system , operon , regulator , burkholderia pseudomallei , microbiology and biotechnology , secretion , regulation of gene expression , burkholderia , regulon , mutant , gene , genetics , bacteria , biochemistry
Type III and type VI secretion systems (T3SSs and T6SSs, respectively) are critical virulence determinants in several Gram-negative pathogens. InBurkholderia 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 thetssAB operon, which was dependent primarily on BprC. VirAG and BprC initiate different transcriptional start sites within T6SS-1, and VirAG is able to activate thehcp1 promoter directly. We also provided novel evidence thatvirAG ,bprC , andtssAB are critical for T6SS-1 function in macrophages. Furthermore,virAG andbprC regulator mutants were avirulent in mice, demonstrating the absolute dependence of T6SS-1 expression on these regulatorsin vivo .