产肠毒素大肠杆菌诱导肠上皮细胞凋亡的研究进展

Research progress in enterotoxigenic Escherichia coli-induced apoptosis of intestinal epithelial cells

摘要:

产肠毒素大肠杆菌(enterotoxigenic Escherichia coli, ETEC)是引起人和动物腹泻的重要病原菌之一，其中黏附素和肠毒素是其感染引起腹泻的主要毒力因子。首先，黏附素介导ETEC与宿主小肠上皮细胞的黏附和定殖。随后，定殖的细菌产生肠毒素，导致水、电解质代谢紊乱，最终引起水样腹泻。传统的观点认为ETEC属于非侵袭性大肠杆菌，并不会引起肠上皮细胞凋亡和破坏肠道的屏障结构。但是越来越多的研究证据表明，在体外和体内ETEC感染均可诱导肠上皮细胞凋亡，破坏宿主肠黏膜屏障的完整性，促进疾病发展。本文将就ETEC不同毒力因子诱导细胞凋亡的具体机制、细胞凋亡与疾病发展的相关性以及在临床如何利用抗凋亡治疗预防ETEC感染等方面进行综述，旨为进一步深入阐明ETEC的分子致病机制提供参考，为防治ETEC引起的腹泻提供新策略。

Abstract:

Adhesins and enterotoxins are the main virulence factors produced by enterotoxigenic Escherichia coli (ETEC), one of the major pathogens causing diarrhea in both humans and animals. Adhesins mediate the initial adhesion of ETEC to intestinal epithelial cells, which leads to ETEC colonization of the host small intestine. Subsequently, the ETEC produces enterotoxins, which result in the loss of electrolytes and culminates in watery diarrhea. ETEC is typically regarded as a non-invasive pathogen, which does not induce the apoptosis of intestinal epithelial cells or destroy intestinal barrier structure. However, more and more evidence indicates that ETEC is able to induce the apoptosis of intestinal epithelial cells in vitro and in vivo. The cell apoptosis would destroy the integrity of the intestinal mucosal barrier of the host and lead to ETEC-caused diarrhea. We introduce the mechanisms of apoptosis induced by different virulence determinants produced by ETEC, the correlation between intestinal epithelial cell apoptosis and ETEC-caused diarrhea, and the potential of using anti-apoptosis therapy to prevent ETEC infection in piglets, aiming to provide a reference for deciphering the molecular pathogenic mechanism of ETEC and provide new measures for preventing and treating diarrhea caused by the pathogen.