Coordinate Control of the Locus of Enterocyte Effacement and Enterohemolysin Genes by Multiple Common Virulence Regulators in Enterohemorrhagic Escherichia coli
Coordinate Control of the Locus of Enterocyte Effacement and Enterohemolysin Genes by Multiple Common Virulence Regulators in Enterohemorrhagic Escherichia coli
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DOI：
10.1128/iai.05023-11
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发表时间：
2011-11-01
影响因子：
3.1
通讯作者：
Ohnishi, Makoto
中科院分区：
文献类型：
--
作者：
Iyoda, Sunao;Honda, Naoko;Ohnishi, Makoto
肠上皮细胞消失位点（LEE）致病岛是肠出血性大肠杆菌（EHEC）与肠上皮细胞紧密粘附所必需的。GrlR和GrlA分别是LEE编码的负调节子和正调节子。这两种调节因子的相互作用对于通过Ler控制LEE基因的转录是重要的，Ler是LEE编码的LEE的中枢激活因子。GrlR-GrlA调节系统不仅控制EHEC中的LEE，而且控制鞭毛和肠溶血素（Ehx）基因的表达。由于Ehx水平在grlR突变体中被显著诱导，但在grlR grlA双突变体中不被显著诱导，并且在ler突变体中通过GrlA的过表达而显著增加，因此GrlA负责这种调节（T. Saitoh等人，J. Bacteriol. 190：4822-4830，2008）。在这项研究中，对ehx基因表达调控的额外研究确定了Ler也作为Ehx表达的激活剂，而不需要GrlA功能。我们最近报道了LysR型调节因子LrhA正控制LEE表达（N.本田等人，摩尔Microbiol. 74：1393-1411，2009）。LrhA突变株的溶血活性低于野生株，LrhA能显著诱导EHEC中ehx基因的转录。coliK-12菌株中表达，表明LrhA在没有GrlA和Ler的情况下也能激活ehx的转录。凝胶迁移率变动分析表明，Ler和LrhA直接结合到ehxC的调控区。总之，这些结果表明ehx的转录受到Ler、GrlA和LrhA的正调控，它们都充当LEE表达的正调控因子。
The locus of enterocyte effacement (LEE) pathogenicity island is required for the intimate adhesion of enterohemorrhagic Escherichia coli (EHEC) to the intestinal epithelial cells. GrlR and GrlA are LEE-encoded negative and positive regulators, respectively. The interaction of these two regulators is important for controlling the transcription of LEE genes through Ler, a LEE-encoded central activator for the LEE. The GrlR-GrlA regulatory system controls not only LEE but also the expression of the flagellar and enterohemolysin (Ehx) genes in EHEC. Since Ehx levels were markedly induced in a grlR mutant but not in a grlR grlA double mutant and significantly increased by overexpression of GrlA in a ler mutant, GrlA is responsible for this regulation (T. Saitoh et al., J. Bacteriol. 190: 4822-4830, 2008). In this study, additional investigations of the regulation of ehx gene expression determined that Ler also acts as an activator for Ehx expression without requiring GrlA function. We recently reported that the LysR-type regulator LrhA positively controls LEE expression (N. Honda et al., Mol. Microbiol. 74: 1393-1411, 2009). The hemolytic activity of the lrhA mutant strain of EHEC was lower than that of the wild-type strain, and LrhA markedly induced ehx transcription in an E. coli K-12 strain, suggesting that LrhA also activates the transcription of ehx without GrlA and Ler. Gel mobility shift assays demonstrated that Ler and LrhA directly bind to the regulatory region of ehxC. Together, these results indicate that transcription of ehx is positively regulated by Ler, GrlA, and LrhA, which all act as positive regulators for LEE expression.