Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation

Autor: Jie Ren, Yu Sang, Ran Qin, Yang Su, Zhongli Cui, Zhiguo Mang, Hao Li, Shaoyong Lu, Jian Zhang, Sen Cheng, Xiaoyun Liu, Jixi Li, Jie Lu, Wenjuan Wu, Guo-Ping Zhao, Feng Shao, Yu-Feng Yao
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 8, Iss 1, Pp 55-69 (2019)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2018.1558963
Popis: ABSTRACTAccumulating 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.
Databáze: Directory of Open Access Journals