National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
Key Laboratory of Molecular Microbiology and Technology, Nankai University, Ministry of Education, Tianjin, China.
Gut Microbes. 2024 Jan-Dec;16(1):2331435. doi: 10.1080/19490976.2024.2331435. Epub 2024 Mar 19.
Enterohemorrhagic (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 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 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.
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），由 CobB 调控，CobB 是细菌中唯一发现的去乙酰化酶。在这里，我们证明 CobB 在 EHEC O157：H7 的毒力中起着重要作用，并且 缺失显著降低了细菌的肠道定植能力。通过乙酰化蛋白质组学研究，我们系统地鉴定了 CobB 可以在 EHEC O157：H7 中调节的几种蛋白质。在这些 CobB 底物中，我们发现 CesA 的 K44 位点的乙酰化，CesA 是 III 型分泌系统（T3SS）转运蛋白 EspA 的伴侣蛋白，削弱了它与 EspA 的结合，从而降低了这种毒力因子的稳定性；这种 PTM 最终减弱了 EHEC O157：H7 的毒力。此外，我们表明，被 CobB 去乙酰化的 K44 位点的去乙酰化促进了 CesA 和 EspA 之间的相互作用，从而增加了细菌的毒力，并在动物实验中。总之，我们表明乙酰化影响 EHEC O157：H7 的毒力，并根据 CesA 去乙酰化的调节，揭示了 CobB 促进细菌毒力的机制。
