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Infect Immun. 2011 Aug;79(8):3064-73. doi: 10.1128/IAI.05148-11. Epub 2011 Jun 13.

Regulation of type VI secretion system during Burkholderia pseudomallei infection.

Author information

1
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.

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.

PMID:
21670170
PMCID:
PMC3147588
DOI:
10.1128/IAI.05148-11
[Indexed for MEDLINE]
Free PMC Article

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