Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
Mol Microbiol. 2011 Oct;82(2):398-415. doi: 10.1111/j.1365-2958.2011.07819.x. Epub 2011 Sep 13.
Ler, encoded by the locus of enterocyte effacement (LEE) of attaching and effacing (A/E) pathogens, induces the expression of LEE genes by counteracting the silencing exerted by H-NS. Ler expression is modulated by several global regulators, and is activated by GrlA, which is also LEE-encoded. Typical enteropathogenic Escherichia coli (EPEC) strains contain the EAF plasmid, which carries the perABC locus encoding PerC. The precise role of PerC in EPEC virulence gene regulation has remained unclear, mainly because EPEC strains lacking the pEAF still express the LEE genes and because PerC is not present in other A/E pathogens such as Citrobacter rodentium. Here, we describe that either PerC or GrlA can independently activate ler expression and, in consequence, of LEE genes depending on the growth conditions. Both PerC and GrlA, with the aid of IHF, counteract the repression exerted by H-NS on ler and can also further increase its activity. Our results substantiate the role of PerC and GrlA in EPEC virulence gene regulation and suggest that these convergent regulatory mechanisms may have represented an evolutionary adaptation in EPEC to co-ordinate the expression of plasmid- and chromosome-encoded virulence factors needed to successfully colonize its intestinal niche.
Ler，由附着和消除（A/E）病原体的肠上皮细胞消失（LEE）基因座编码，通过抵消 H-NS 施加的沉默来诱导 LEE 基因的表达。Ler 的表达受几种全局调节剂调节，并由 GrlA 激活，GrlA 也是 LEE 编码的。典型的肠致病性大肠杆菌（EPEC）菌株含有 EAF 质粒，该质粒携带编码 PerC 的 perABC 基因座。PerC 在 EPEC 毒力基因调控中的精确作用仍不清楚，主要是因为缺乏 pEAF 的 EPEC 菌株仍表达 LEE 基因，并且 PerC 不存在于其他 A/E 病原体如鼠柠檬酸杆菌。在这里，我们描述了 PerC 或 GrlA 可以独立激活 ler 的表达，从而取决于生长条件，激活 LEE 基因。PerC 和 GrlA 都在 IHF 的帮助下，抵消了 H-NS 对 ler 的抑制作用，并且还可以进一步增加其活性。我们的结果证实了 PerC 和 GrlA 在 EPEC 毒力基因调控中的作用，并表明这些收敛的调控机制可能是 EPEC 为协调成功定殖其肠道生态位所需的质粒和染色体编码毒力因子的表达而进行的一种进化适应。
