Open AccessMethylation of PhoP by CheR Regulates Salmonella Virulence
Author(s) -
Yang Su,
Jianhui Li,
Wenting Zhang,
Jinjing Ni,
Rui Huang,
Zuoqiang Wang,
Sen Cheng,
Yue Wang,
Zhixin Tian,
Qiuxiang Zhou,
Donghai Lin,
Wenjuan Wu,
Christoph M. Tang,
Xiaoyun Liu,
Jie Lu,
Yufeng Yao
Publication year - 2021
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.02099-21
Subject(s) - virulence , methylation , methyltransferase , salmonella enterica , protein methylation , biochemistry , phosphorylation , dna methylation , response regulator , chemotaxis , chemistry , salmonella , dna , biology , bacteria , gene , genetics , escherichia coli , gene expression , mutant , receptor
The two-component system PhoP/PhoQ is essential for Salmonella enterica serovar Typhimurium virulence. Here, we report that PhoP is methylated extensively. Two consecutive glutamate (E) and aspartate (D)/E residues, i.e., E8/D9 and E107/E108, and arginine (R) 112 can be methylated. Individual mutation of these above-mentioned residues caused impaired phosphorylation and dimerization or DNA-binding ability of PhoP to a different extent and led to attenuated bacterial virulence. With the help of specific antibodies recognizing methylated E8 and monomethylated R112, we found that the methylation levels of E8 or R112 decreased dramatically when bacteria encountered low magnesium, acidic pH, or phagocytosis by macrophages, under which PhoP can be activated. Furthermore, CheR, a bacterial chemotaxis methyltransferase, was identified to methylate R112. Overexpression of cheR decreased PhoP activity but increased PhoP stability. Together, the current study reveals that methylation plays an important role in regulating PhoP activities in response to environmental cues and, consequently, modulates Salmonella virulence.