Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.
Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.
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DOI：
10.1371/journal.ppat.1004933
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发表时间：
2015-05
期刊：
影响因子：
6.7
通讯作者：
Yildiz FH
中科院分区：
文献类型：
--
作者：
Cheng AT;Ottemann KM;Yildiz FH
双组分信号转导系统（TCS）被细菌用来感知和响应它们的环境。TCS通常由传感器组胺酸激酶（HK）和反应调节因子（RR）组成。霍乱弧菌基因组编码52个RR，但这些RR在霍乱弧菌发病机制中的作用在很大程度上是未知的。为了鉴定控制霍乱弧菌定殖的RR，产生每个RR的框内缺失，并使用幼小鼠肠定殖测定分析所得突变体。我们发现52个RR中有12个参与肠道定植。突变体缺乏一个以前未表征的RR，VCA0566（更名为BRR B），表现出显着的殖民缺陷。进一步的实验表明，在预测的保守天冬氨酸上的AlpyrB磷酸化状态有助于肠道定植。使用全基因组表达分析来确定EhrB调节子。它由几个基因组成，包括那些创建VI型分泌系统（T6SS）的基因。我们使用几种体外测定和细菌杀伤测定确定了T6SS表达所需的BptrB，并且还确定了T6SS是肠道定植所需的。vxrB在四基因操纵子中编码，并且其他vxr操纵子成员也调节肠定殖。最后，尽管ΔvxrB在单菌株肠道定植中表现出缺陷，但ΔvxrB菌株未表现出任何体外生长缺陷。总的来说，我们的工作表明，一小组的RR是必需的肠道定植和这些监管机构之一，ARB影响定植至少部分通过其调节T6SS基因。病原菌在感染人类宿主期间经历不同的条件，并且通常使用双组分信号转导系统（TCS）来监测其环境。TCS由组氨酸激酶（HK）和相应的反应调节因子（RR）组成，前者感知环境信号，后者介导细胞反应。人类病原体霍乱弧菌的基因组含有编码HK和RR蛋白的大量基因。在本研究中，我们系统地分析了每种霍乱弧菌RR在发病机制中的作用。我们确定了一个以前没有特点的RR，BURB，作为一个新的毒力因子。我们证明了BpyrB控制VI型分泌系统（T6SS）的表达，这是一种毒力纳米机器，可直接将效应子易位到细菌或宿主细胞中，从而通过与姐妹细胞和肠道微生物群竞争来促进定植。本研究首次系统分析了所有RRs在霍乱弧菌发病机制中的作用，为了解控制霍乱弧菌发病的信号转导途径提供了基础。
Two-component signal transduction systems (TCS) are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK) and a response regulator (RR). The Vibrio cholerae genome encodes 52 RR, but the role of these RRs in V. cholerae pathogenesis is largely unknown. To identify RRs that control V. cholerae colonization, in-frame deletions of each RR were generated and the resulting mutants analyzed using an infant mouse intestine colonization assay. We found that 12 of the 52 RR were involved in intestinal colonization. Mutants lacking one previously uncharacterized RR, VCA0566 (renamed VxrB), displayed a significant colonization defect. Further experiments showed that VxrB phosphorylation state on the predicted conserved aspartate contributes to intestine colonization. The VxrB regulon was determined using whole genome expression analysis. It consists of several genes, including those genes that create the type VI secretion system (T6SS). We determined that VxrB is required for T6SS expression using several in vitro assays and bacterial killing assays, and furthermore that the T6SS is required for intestinal colonization. vxrB is encoded in a four gene operon and the other vxr operon members also modulate intestinal colonization. Lastly, though ΔvxrB exhibited a defect in single-strain intestinal colonization, the ΔvxrB strain did not show any in vitro growth defect. Overall, our work revealed that a small set of RRs is required for intestinal colonization and one of these regulators, VxrB affects colonization at least in part through its regulation of T6SS genes. Pathogenic bacteria experience varying conditions during infection of human hosts and often use two-component signal transduction systems (TCSs) to monitor their environment. TCS consists of a histidine kinase (HK), which senses environmental signals, and a corresponding response regulator (RR), which mediates a cellular response. The genome of the human pathogen V. cholerae contains a multitude of genes encoding HKs and RRs proteins. In the present study, we systematically analyzed the role of each V. cholerae RR for its role in pathogenesis. We identified a previously uncharacterized RR, VxrB, as a new virulence factor. We demonstrated that VxrB controls expression of the type VI secretion system (T6SS), a virulence nanomachine that directly translocates effectors into bacterial or host cells, thereby facilitating colonization by competing with sister cells and intestinal microbiota. This study represents the first systematic analysis of the role of all RRs in V. cholerae pathogenesis and provides a foundation for understanding the signal transduction pathways controlling V. cholerae pathogenesis.
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影响因子：
3.2
作者：
Beyhan, Sinem;Bilecen, Kivanc;Yildiz, Fitnat H.
通讯作者：
Yildiz, Fitnat H.
影响因子：
3.6
作者：
Correa, NE;Lauriano, CM;Klose, KE
通讯作者：
Klose, KE
DOI：
10.1126/science.1222981
发表时间：
2012-07-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Berk V;Fong JC;Dempsey GT;Develioglu ON;Zhuang X;Liphardt J;Yildiz FH;Chu S
通讯作者：
Chu S
影响因子：
3.1
作者：
Ishikawa, Takahiko;Sabharwal, Dharmesh;Wai, Sun Nyunt
通讯作者：
Wai, Sun Nyunt
影响因子：
3.2
作者：
Hussa, Elizabeth A.;O'Shea, Therese M.;Visickl, Karen L.
通讯作者：
Visickl, Karen L.