Department of Bacteriology, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi Maebashi, Gunma, 371-8511, Japan.
Department of Infectious Diseases and Host Defense, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi Maebashi, Gunma, 371-8511, Japan.
Sci Rep. 2020 Sep 23;10(1):15173. doi: 10.1038/s41598-020-72412-w.
The Tol-Pal system is a protein complex that is highly conserved in many gram-negative bacteria. We show here that the Tol-Pal system is associated with the enteric pathogenesis of enterohemorrhagic E. coli (EHEC). Deletion of tolB, which is required for the Tol-Pal system decreased motility, secretion of the Type III secretion system proteins EspA/B, and the ability of bacteria to adhere to and to form attaching and effacing (A/E) lesions in host cells, but the expression level of LEE genes, including espA/B that encode Type III secretion system proteins were not affected. The Citrobacter rodentium, tolB mutant, that is traditionally used to estimate Type III secretion system associated virulence in mice did not cause lethality in mice while it induced anti-bacterial immunity. We also found that the pal mutant, which lacks activity of the Tol-Pal system, exhibited lower motility and EspA/B secretion than the wild-type parent. These combined results indicate that the Tol-Pal system contributes to the virulence of EHEC associated with the Type III secretion system and flagellar activity for infection at enteric sites. This finding provides evidence that the Tol-Pal system may be an effective target for the treatment of infectious diseases caused by pathogenic E. coli.
托尔-帕尔系统是一种在许多革兰氏阴性菌中高度保守的蛋白质复合物。我们在这里表明，托尔-帕尔系统与肠出血性大肠杆菌（EHEC）的肠致病性有关。缺失 tolB 会降低细菌的运动性、III 型分泌系统蛋白 EspA/B 的分泌以及细菌黏附和形成附着和破坏（A/E）病变的能力，但不影响包括编码 III 型分泌系统蛋白的 espA/B 在内的 LEE 基因的表达水平。传统上用于估计 III 型分泌系统相关毒力的鼠柠檬酸杆菌 tolB 突变体在小鼠中不会引起致死性，但会诱导抗细菌免疫。我们还发现，缺乏托尔-帕尔系统活性的 pal 突变体的运动性和 EspA/B 分泌均低于野生型亲本。这些综合结果表明，托尔-帕尔系统有助于与 III 型分泌系统和鞭毛活性相关的 EHEC 的毒力，以感染肠道部位。这一发现为托尔-帕尔系统可能成为治疗致病性大肠杆菌引起的传染病的有效靶点提供了证据。
