Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Mol Microbiol. 2021 Jul;116(1):168-183. doi: 10.1111/mmi.14698. Epub 2021 Mar 2.
Enterohemorrhagic Escherichia coli (EHEC), an enteropathogen that colonizes in the intestine, causes severe diarrhea and hemorrhagic colitis in humans by the expression of the type III secretion system (T3SS) and Shiga-like toxins (Stxs). However, how EHEC can sense and respond to the changes in the alimentary tract and coordinate the expression of these virulence genes remains elusive. The T3SS-related genes are known to be regulated by the locus of enterocyte effacement (LEE)-encoded regulators, such as Ler, as well as non-LEE-encoded regulators in response to different environmental cues. Herein, we report that OmpR, which participates in the adaptation of E. coli to osmolarity and pH alterations, is required for EHEC infection in Caenorhabditis elegans. OmpR protein was able to directly bind to the promoters of ler and stx1 (Shiga-like toxin 1) and regulate the expression of T3SS and Stx1, respectively, at the transcriptional level. Moreover, we demonstrated that the expression of ler in EHEC is in response to the intestinal environment and is regulated by OmpR in C. elegans. Taken together, we reveal that OmpR is an important regulator of EHEC which coordinates the expression of virulence factors during gastrointestinal infection in vivo.
肠出血性大肠杆菌（EHEC）是一种定植于肠道的肠道病原体，通过表达 III 型分泌系统（T3SS）和志贺样毒素（Stxs）在人类中引起严重腹泻和出血性结肠炎。然而，EHEC 如何感知和响应消化道的变化并协调这些毒力基因的表达仍然难以捉摸。已知 T3SS 相关基因受肠上皮细胞消失（LEE）编码调节剂的调节，如 Ler，以及非 LEE 编码调节剂，以响应不同的环境线索。在此，我们报告称，参与大肠杆菌适应渗透压和 pH 值变化的 OmpR 对于在秀丽隐杆线虫中感染 EHEC 是必需的。OmpR 蛋白能够直接结合 ler 和 stx1（志贺样毒素 1）的启动子，并分别在转录水平上调节 T3SS 和 Stx1 的表达。此外，我们证明了 EHEC 中 ler 的表达是对肠道环境的反应，并在秀丽隐杆线虫中受 OmpR 调节。总之，我们揭示了 OmpR 是 EHEC 的一个重要调节因子，它在体内胃肠道感染过程中协调毒力因子的表达。
