Activation of Motility by Sensing Short-Chain Fatty Acids via Two Steps in a Flagellar Gene Regulatory Cascade in Enterohemorrhagic Escherichia coli
Activation of Motility by Sensing Short-Chain Fatty Acids via Two Steps in a Flagellar Gene Regulatory Cascade in Enterohemorrhagic Escherichia coli
复制标题
DOI：
10.1128/iai.00927-10
复制
发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
Sugimoto, Nakaba
中科院分区：
文献类型：
--
作者：
Tobe, Toru;Nakanishi, Noriko;Sugimoto, Nakaba
毒力基因的调控表达对于肠道病原体的成功感染至关重要。细菌依靠感知环境信号来寻找合适的生态位并达到感染状态。经口摄入的肠出血性大肠杆菌（EHEC）通过胃肠道传播，并遇到各种环境因素，其中一些作为诱导毒力基因的触发信号。丁酸是一种主要的短链脂肪酸（SCFAs），它是一种信号，可以增强亲密附着和III型分泌基因的表达。我们进一步探索了SCFAs的作用，发现SCFAs对鞭毛表达有积极作用。虽然EHEC在Dulbecco改良Eagle培养基（DMEM）（一种增强毒力基因表达的组织培养基）中生长时不产生鞭毛，但向培养基中添加SCFA诱导鞭毛的产生，EHEC细菌变得能动。在SCFA中，丁酸盐同时激活毒力基因和鞭毛基因。鞭毛不影响初始粘附，并且它们在小菌落形成期间不表达于粘附细菌中。SCFAs通过两个调节步骤激活鞭毛基因。丁酸通过亮氨酸应答调节蛋白（Lrp）激活flhDC调节基因，Lrp也是毒力基因的调节因子。然而，丁酸盐、乙酸盐和丙酸盐也独立于flhDC活化而活化下游基因。因此，当在肠道中遇到浓度增加的SCFA（富含乙酸盐）时，EHEC首先激活鞭毛产生和运动性，然后激活参与粘附和III型分泌的基因，这导致在优选的生态位中有效粘附。
The regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. Orally ingested enterohemorrhagic Escherichia coli (EHEC) travels through the gastrointestinal tract and encounters a variety of environmental factors, some of which act as triggering signals for the induction of virulence genes. Butyrate, one of the main short-chain fatty acids (SCFAs), is such a signal, enhancing the expression of genes for intimate attachment and type III secretion. We further explored the role of SCFAs and found a positive effect of SCFAs on flagellar expression. Although EHEC did not produce flagella when grown in Dulbecco's modified Eagle's medium (DMEM), a tissue culture medium that enhances virulence gene expression, the addition of SCFAs to the medium induced the production of flagella, and the EHEC bacteria became motile. Among SCFAs, butyrate simultaneously activates both virulence and flagellar genes. Flagella did not affect initial adherence, and they were not expressed in adherent bacteria during microcolony formation. SCFAs activated flagellar genes via two regulatory steps. Butyrate activated the flhDC regulatory genes through leucine-responsive regulatory protein (Lrp), which is also a regulator of virulence genes. However, butyrate, acetate, and propionate also activated downstream genes independently of flhDC activation. Consequently, when encountering increased concentrations of SCFAs, which are abundant in acetate, in the intestine, EHEC first activates flagellar production and motility, followed by genes involved in adherence and type III secretion, which leads to efficient adherence in a preferable niche.