文献类型：期刊文献

英文题名：Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation

作者：Ren, Jie[1];Sang, Yu[1];Qin, Ran[2];Su, Yang[1];Cui, Zhongli[2];Mang, Zhiguo[3];Li, Hao[3];Lu, Shaoyong[4];Zhang, Jian[4];Cheng, Sen[5,6];Liu, Xiaoyun[5,6];Li, Jixi[7];Lu, Jie[8];Wu, Wenjuan[9];Zhao, Guo-Ping[10];Shao, Feng[11];Yao, Yu-Feng[1,9]

机构：[1]Shanghai Jiao Tong Univ, Inst Med Sci, Dept Microbiol & Immunol, Lab Bacterial Pathogenesis,Sch Med, Shanghai 200025, Peoples R China;[2]Nanjing Agr Univ, Coll Life Sci, Key Lab Agr Environm Microbiol, Minist Agr, Nanjing, Jiangsu, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut Sci, Shanghai, Peoples R China;[4]Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Sch Med, Dept Pathophysiol,Chinese Minist Educ, Shanghai, Peoples R China;[5]Peking Univ, Coll Chem & Mol Engn, Inst Analyt Chem, Beijing, Peoples R China;[6]Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Beijing, Peoples R China;[7]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;[8]Shanghai Ruijin Hosp, Dept Infect Dis, Shanghai, Peoples R China;[9]Tongji Univ, Shanghai East Hosp, Sch Med, Dept Lab Med, Shanghai 200120, Peoples R China;[10]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Synthet Biol, Shanghai, Peoples R China;[11]Natl Inst Biol Sci, Beijing, Peoples R China

年份：2019

卷号：8

期号：1

起止页码：55

外文期刊名：EMERGING MICROBES & INFECTIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000455807500007)】；

基金：4This work was supported by National Natural Science Foundation of China [grant number 31700120,81501733, 81772140,81830068]; Ministry of Science and Technology of the People's Republic of China [grant number 2016YFA0500600]; the State Key Development Programs for Basic Research of China [grant number 2015CB554203]; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning.

语种：英文

外文关键词：Acetyl phosphate; acetylation; phosphorylation; PhoP; virulence; metabolism

摘要：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.