Abstract：
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen that specifically colonizes and infects the human large intestine. EHEC O157:H7 engages intricate regulatory pathways to detect host intestinal signals and regulate virulence-related gene expression during colonization and infection. However, the overall EHEC O157:H7 virulence regulatory network in the human large intestine remains incompletely understood. Here, we report a complete signal regulatory pathway where the EvgSA two-component system responds to high-nicotinamide levels produced by microbiota in the large intestine and directly activates loci of enterocyte effacement genes to promote EHEC O157:H7 adherence and colonization. This EvgSA-mediated nicotinamide signaling regulatory pathway is conserved and widespread among several other EHEC serotypes. Moreover, disruption of this virulence-regulating pathway by the deletion of evgS or evgA significantly decreased EHEC O157:H7 adherence and colonization in the mouse intestinal tract, indicating that these genes could be potential targets for the development of new therapeutics for EHEC O157:H7 infection.
摘要：
肠出血性大肠杆菌（EHEC）O157：H7是一种食源性病原体，可特异性定植和感染人类大肠。EHECO157：H7参与复杂的调节途径来检测宿主肠道信号并在定植和感染期间调节毒力相关基因表达。然而,人类大肠EHECO157:H7毒力调控网络的总体情况尚不完全清楚.这里,我们报道了一个完整的信号调节途径,在该途径中,EvgSA双组分系统对大肠中微生物群产生的高烟酰胺水平作出反应,并直接激活肠细胞脱落基因位点,以促进EHECO157:H7粘附和定植.这种EvgSA介导的烟酰胺信号传导调节途径在几种其他EHEC血清型中是保守和广泛的。此外，通过删除evgS或evgA破坏该毒力调节途径显着降低了EHECO157：H7在小鼠肠道中的粘附和定植，表明这些基因可能是开发EHECO157：H7感染新疗法的潜在靶标。
