Title | Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation |
Authors | Ren, Jie Sang, Yu Qin, Ran Su, Yang Cui, Zhongli Mang, Zhiguo Li, Hao Lu, Shaoyong Zhang, Jian Cheng, Sen Liu, Xiaoyun Li, Jixi Lu, Jie Wu, Wenjuan Zhao, Guo-Ping Shao, Feng Yao, Yu-Feng |
Affiliation | Shanghai Jiao Tong Univ, Inst Med Sci, Dept Microbiol & Immunol, Lab Bacterial Pathogenesis,Sch Med, Shanghai 200025, Peoples R China Nanjing Agr Univ, Coll Life Sci, Key Lab Agr Environm Microbiol, Minist Agr, Nanjing, Jiangsu, Peoples R China East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut Sci, Shanghai, Peoples R China Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Sch Med, Dept Pathophysiol,Chinese Minist Educ, Shanghai, Peoples R China Peking Univ, Coll Chem & Mol Engn, Inst Analyt Chem, Beijing, Peoples R China Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Beijing, Peoples R China Fudan Univ, Shanghai Engn Res Ctr Ind Microorganisms, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci,State Key Lab Genet Engn, Shanghai, Peoples R China Shanghai Ruijin Hosp, Dept Infect Dis, Shanghai, Peoples R China Tongji Univ, Shanghai East Hosp, Sch Med, Dept Lab Med, Shanghai 200120, Peoples R China Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Synthet Biol, Shanghai, Peoples R China Natl Inst Biol Sci, Beijing, Peoples R China |
Keywords | Acetyl phosphate acetylation phosphorylation PhoP virulence metabolism |
Issue Date | 2019 |
Publisher | EMERGING MICROBES & INFECTIONS |
Abstract | Accumulating evidence indicates that bacterial metabolism plays an important role in virulence. Acetyl phosphate (AcP), the high-energy intermediate of the phosphotransacetylase-acetate kinase pathway, is the major acetyl donor in E. coli. PhoP is an essential transcription factor for bacterial virulence. Here, we show in Salmonella typhimurium that PhoP is non-enzymatically acetylated by AcP, which modifies its transcriptional activity, demonstrating that the acetylation of Lysine 102 (K102) is dependent on the intracellular AcP. The acetylation level of K102 decreases under PhoP-activating conditions including low magnesium, acid stress or following phagocytosis. Notably, in vitro assays show that K102 acetylation affects PhoP phosphorylation and inhibits its transcriptional activity. Both cell and mouse models show that K102 is critical to Salmonella virulence, and suggest acetylation is involved in regulating PhoP activity. Together, the current study highlights the importance of the metabolism in bacterial virulence, and shows AcP might be a key mediator. |
URI | http://hdl.handle.net/20.500.11897/551429 |
ISSN | 2222-1751 |
DOI | 10.1080/22221751.2018.1558963 |
Indexed | SCI(E) |
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