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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