PDF(Pubmed)
Abstract：
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a common food-borne pathogen that can cause acute diseases. Lysine acetylation is a post-translational modification (PTM) that occurs in various prokaryotes and is regulated by CobB, the only deacetylase found in bacteria. Here, we demonstrated that CobB plays an important role in the virulence of EHEC O157:H7 and that deletion of cobB significantly decreased the intestinal colonization ability of bacteria. Using acetylation proteomic studies, we systematically identified several proteins that could be regulated by CobB in EHEC O157:H7. Among these CobB substrates, we found that acetylation at the K44 site of CesA, a chaperone for the type-III secretion system (T3SS) translocator protein EspA, weakens its binding to EspA, thereby reducing the stability of this virulence factor; this PTM ultimately attenuating the virulence of EHEC O157:H7. Furthermore, we showed that deacetylation of the K44 site, which is deacetylated by CobB, promotes the interaction between CesA and EspA, thereby increasing bacterial virulence in vitro and in animal experiments. In summary, we showed that acetylation influences the virulence of EHEC O157:H7, and uncovered the mechanism by which CobB contributes to bacterial virulence based on the regulation of CesA deacetylation.
摘要：
肠出血性大肠杆菌（EHEC）O157：H7是一种常见的食源性病原体，可引起急性疾病。赖氨酸乙酰化是一种发生在各种原核生物中的翻译后修饰（PTM），受CobB调节，细菌中唯一的脱乙酰酶.这里,我们证明了CobB在EHECO157：H7的毒力中起重要作用，并且删除cobB显着降低了细菌的肠道定植能力。使用乙酰化蛋白质组学研究，我们系统地鉴定了EHECO157:H7中可能受CobB调节的几种蛋白质。在这些CobB底物中,我们发现CesA的K44位点发生乙酰化,III型分泌系统（T3SS）转运蛋白EspA的伴侣，削弱了它与EspA的结合,从而降低该毒力因子的稳定性;该PTM最终减弱EHECO157:H7的毒力。此外，我们发现K44位点的脱乙酰化，它被CobB去乙酰化，促进了CesA和EspA之间的相互作用，从而在体外和动物实验中增加细菌毒力。总之,我们表明乙酰化会影响EHECO157：H7的毒力，并基于CesA脱乙酰化的调节揭示了CobB促进细菌毒力的机制。
