Regulation of Type VI Secretion System during Burkholderia pseudomallei Infection
Regulation of Type VI Secretion System during Burkholderia pseudomallei Infection
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DOI：
10.1128/iai.05148-11
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发表时间：
2011-08-01
影响因子：
3.1
通讯作者：
Gan, Yunn-Hwen
中科院分区：
文献类型：
--
作者：
Chen, Yahua;Wong, Jocelyn;Gan, Yunn-Hwen
III型和VI型分泌系统（分别为T3 SS和T6 SS）是几种革兰氏阴性病原体中的关键毒力决定因子。在类鼻疽伯克霍尔德菌中，T3 SS-3和T6 SS-1簇与哺乳动物宿主中的细菌毒力有关。我们最近发现了一个调节级联，协调控制T3 SS-3和T6 SS-1的表达。BsaN是位于T3 SS-3内的中心调节子，用于表达T3 SS-3效应子和T6 SS-1的调节子，如VirA-VirG（VirAG）和BprC。而T6 SS-1基因的表达是完全依赖于BprC细菌生长在培养基中，宿主细胞内的表达是依赖于两个组件的传感器调节VirAG，除了tssAB操纵子，这是主要依赖于BprC。VirAG和BprC在T6 SS-1中启动不同的转录起始位点，并且VirAG能够直接激活hcp 1启动子。我们还提供了新的证据，证明virAG，bprC和tssAB对巨噬细胞中的T6 SS-1功能至关重要。此外，virAG和bprC调节突变体在小鼠中是无毒的，证明了T6 SS-1表达在体内对这些调节的绝对依赖性。
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.