Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic acid, host cell adherence, invasion, and in vivo colonization.
Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic acid, host cell adherence, invasion, and in vivo colonization.
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DOI：
10.1371/journal.pone.0042842
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fox JG
中科院分区：
文献类型：
--
作者：
Lertpiriyapong K;Gamazon ER;Feng Y;Park DS;Pang J;Botka G;Graffam ME;Ge Z;Fox JG
最近发现的变形菌VI型分泌系统（T6 SS）已被证明可以促进致病性，竞争优势，竞争微生物，并适应环境扰动。通过详细的表型特征的功能丧失突变体，在硅片，在体外和体内分析，我们提供的证据表明，肠道病原体，空肠弯曲菌，具有功能性T6 SS和分泌系统发挥多效性作用的两个关键过程-生存在胆汁盐，脱氧胆酸（DCA），宿主细胞粘附和入侵。在初始暴露于较高生理水平的DCA（0.075%-0.2%）时，T6 SS的表达对C.空肠增殖，而下调或失活T6 SS使C.空肠抵抗这种作用。梭空肠多药外排转运蛋白基因cmeA在DCA初始暴露期间在野生型C中显著上调。空肠相对于T6 SS缺陷型菌株，表明增殖抑制是T6 SS介导的DCA流入的结果。外排转运蛋白活性和T6 SS的顺序调节部分代表了C.空肠以克服这种抑制作用，从而确保其存活。C.空肠T6 SS在宿主细胞粘附和侵袭中起重要作用，因为T6 SS失活导致体外细胞系的粘附和侵袭减少，而编码分泌的T6 SS组分的溶血素共调节蛋白的过表达极大地增强了这些过程。接种B6.129P2-IL-10 tm 1Cgn小鼠后，T6 SS缺陷型C.空肠菌株没有有效地建立持久的定植，表明T6 SS有助于体内定植。综上所述，我们的数据证明了细菌T6 SS在宿主细胞粘附、侵袭、定殖中的重要性，并且据我们所知，第一次适应DCA，为T6 SS在C.空肠发病机制
The recently identified type VI secretion system (T6SS) of proteobacteria has been shown to promote pathogenicity, competitive advantage over competing microorganisms, and adaptation to environmental perturbation. By detailed phenotypic characterization of loss-of-function mutants, in silico, in vitro and in vivo analyses, we provide evidence that the enteric pathogen, Campylobacter jejuni, possesses a functional T6SS and that the secretion system exerts pleiotropic effects on two crucial processes – survival in a bile salt, deoxycholic acid (DCA), and host cell adherence and invasion. The expression of T6SS during initial exposure to the upper range of physiological levels of DCA (0.075%–0.2%) was detrimental to C. jejuni proliferation, whereas down-regulation or inactivation of T6SS enabled C. jejuni to resist this effect. The C. jejuni multidrug efflux transporter gene, cmeA, was significantly up-regulated during the initial exposure to DCA in the wild type C. jejuni relative to the T6SS-deficient strains, suggesting that inhibition of proliferation is the consequence of T6SS-mediated DCA influx. A sequential modulation of the efflux transporter activity and the T6SS represents, in part, an adaptive mechanism for C. jejuni to overcome this inhibitory effect, thereby ensuring its survival. C. jejuni T6SS plays important roles in host cell adhesion and invasion as T6SS inactivation resulted in a reduction of adherence to and invasion of in vitro cell lines, while over-expression of a hemolysin co-regulated protein, which encodes a secreted T6SS component, greatly enhanced these processes. When inoculated into B6.129P2-IL-10tm1Cgn mice, the T6SS-deficient C. jejuni strains did not effectively establish persistent colonization, indicating that T6SS contributes to colonization in vivo. Taken together, our data demonstrate the importance of bacterial T6SS in host cell adhesion, invasion, colonization and, for the first time to our knowledge, adaptation to DCA, providing new insights into the role of T6SS in C. jejuni pathogenesis.
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影响因子：
3.1
作者：
Chen, Ming L.;Ge, Zhongming;Schauer, David B.
通讯作者：
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影响因子：
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DOI：
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