Antimicrobial peptides activate the Vibrio cholerae σE regulon through an OmpU-dependent signalling pathway
Antimicrobial peptides activate the Vibrio cholerae σE regulon through an OmpU-dependent signalling pathway
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DOI：
10.1111/j.1365-2958.2006.05544.x
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Waldor, Matthew K.
中科院分区：
文献类型：
--
作者：
Mathur, Jyoti;Davis, Brigid M.;Waldor, Matthew K.
霍乱弧菌是一种肠道致病菌，它受到几种膜作用的宿主肠道来源的抗菌肽（AP）的攻击。我们以前发现，一个主要的霍乱弧菌外膜蛋白，OmpU，赋予耐多粘菌素B和生物活性肽（P2）来自人类杀菌/渗透性增加蛋白。在这里，我们报告说，替代σ因子σ（E）也发挥了关键作用，在确定霍乱弧菌耐AP和OmpU和σ（E）位于相同的途径。事实上，我们发现OmpU是基础sigma（E）表达的关键决定因素。我们还发现，亚致死AP暴露激活sigma（E）和sigma（E）介导的周质应激反应。在缺乏OmpU或DegS（一种控制σ（E）活性的周质蛋白酶）的霍乱弧菌细胞中，σ（E）不被P2激活。在OmpU的推定DegS结合残基中具有点突变的菌株中缺乏AP引起的sigma（E）活化为OmpU和DegS介导的sigma（E）活化之间的联系提供了支持。我们认为AP诱导的膜扰动改变了OmpU的构象，从而触发了DegS依赖的sigma（E）激活级联反应。因此，OmpU似乎在信号转导途径中充当传感器组分。
Vibrio cholerae, an enteric pathogen, is subject to assault by several membrane-acting, host gut-derived antimicrobial peptides (AP). We previously found that a major V. cholerae outer membrane protein, OmpU, confers resistance to polymyxin B and to a bioactive peptide (P2) derived from the human bactericidal/permeability-increasing protein. Here, we report that the alternative sigma factor sigma(E) also plays a critical role in determining V. cholerae resistance to AP and that OmpU and sigma(E) lie in the same pathway. In fact, we found that OmpU is a key determinant of basal sigma(E) expression. We also found that sublethal AP exposure activates sigma(E) and the sigma(E)-mediated periplasmic stress response. sigma(E) is not activated by P2 in V. cholerae cells lacking OmpU or DegS, a periplasmic protease that controls sigma(E) activity. The lack of AP-elicited sigma(E) activation in a strain harbouring a point mutation in OmpU's putative DegS-binding residues provides support for a link between OmpU and DegS-mediated activation of sigma(E). We propose that AP-induced membrane perturbations change the conformation of OmpU to trigger a DegS-dependent sigma(E)-activating cascade. Thus, OmpU appears to act as a sensor component in a signal transduction pathway.