The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7.

The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7.
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DOI:
10.1111/mmi.12651
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发表时间:
2014-07
影响因子:
3.6
通讯作者:
Roe AJ
Roe AJ
中科院分区:
生物学2区
文献类型:
--
作者:
Beckham KS;Connolly JP;Ritchie JM;Wang D;Gawthorne JA;Tahoun A;Gally DL;Burgess K;Burchmore RJ;Smith BO;Beatson SA;Byron O;Wolfe AJ;Douce GR;Roe AJ

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经典的研究集中在单个调控因子在控制毒力基因表达中的作用。然而,一个新的主题是细菌代谢在这一过程中也起着关键作用。我们之前的工作确定了一系列与毒力调节有关的蛋白质。这些蛋白质之一是AdhE,一种双功能乙酰辅酶A脱氢酶和醇脱氢酶。其基因(adhE)的缺失导致细胞外乙酸水平升高和明显的多效性表型:强烈抑制三型分泌系统(T3SS)和过度表达的非功能性鞭毛。相应地,adhE突变体与宿主细胞结合不良,无法游泳。此外,突变体的毒性显着低于它的父母在体内测试时,这支持的假设,即附着和运动是中央的殖民过程。AdhE影响毒力基因调控的分子基础被认为是多因素的,涉及乙酸盐刺激的鞭毛表达的转录和转录后调节的T3SS通过Hfq。我们的研究揭示了细菌生理学,毒力基因的表达和这些过程受到调节的潜在分子机制之间的联系。
Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is that bacterial metabolism also plays a key role in this process. Our previous work identified a series of proteins that were implicated in the regulation of virulence. One of these proteins was AdhE, a bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion of its gene (adhE) resulted in elevated levels of extracellular acetate and a stark pleiotropic phenotype: strong suppression of the Type Three Secretion System (T3SS) and overexpression of non-functional flagella. Correspondingly, the adhE mutant bound poorly to host cells and was unable to swim. Furthermore, the mutant was significantly less virulent than its parent when tested in vivo, which supports the hypothesis that attachment and motility are central to the colonization process. The molecular basis by which AdhE affects virulence gene regulation was found to be multifactorial, involving acetate-stimulated transcription of flagella expression and post-transcriptional regulation of the T3SS through Hfq. Our study reveals fascinating insights into the links between bacterial physiology, the expression of virulence genes, and the underlying molecular mechanism mechanisms by which these processes are regulated.
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