CobB-mediated deacetylation of the chaperone CesA regulates Escherichia coli O157:H7 virulence

• Published in: Gut microbes Vol. 16; no. 1; p. 2331435
• Main Authors: Li, Linxing, Yang, Bin, Wang, Jing, Wei, Yi, Xiang, Binbin, Liu, Yutao, Wu, Pan, Li, Wanwu, Wang, Yanling, Zhao, Xinyu, Qin, Jingliang, Liu, Miaomiao, Liu, Ruiying, Ma, Guozhen, Fu, Tian, Wang, Min, Liu, Bin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2024; Taylor & Francis Group
• Subjects: Animals; CesA; CobB; deacetylation; EHEC; Escherichia coli Infections - microbiology; Escherichia coli O157 - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; EspA; Gastrointestinal Microbiome; Proteomics; Research Paper; Virulence; EHEC; virulence; CobB; deacetylation; EspA; CesA
• ISSN: 1949-0976; 1949-0984; 1949-0984
• DOI: 10.1080/19490976.2024.2331435

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.