| Title | Methylation of PhoP by CheR Regulates Salmonella Virulence |
| Authors | Su, Yang Li, Jianhui Zhang, Wenting Ni, Jinjing Huang, Rui Wang, Zuoqiang Cheng, Sen Wang, Yue Tian, Zhixin Zhou, Qiuxiang Lin, Donghai Wu, Wenjuan Tang, Christoph M. Liu, Xiaoyun Lu, Jie Yao, Yu-Feng |
| Affiliation | Shanghai Jiao Tong Univ, Dept Microbiol & Immunol, Lab Bacterial Pathogenesis, Sch Med, Shanghai, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Microbiol, Hlth Sci Ctr, Beijing, Peoples R China Tongji Univ, Sch Chem Sci & Engn, Shanghai Key Lab Chem Assessment & Sustainabil, Shanghai, Peoples R China Xiamen Univ, Coll Chem & Chem Engn, Xiamen, Peoples R China Tongji Univ, Shanghai East Hosp, Dept Lab Med, Sch Med, Shanghai, Peoples R China Univ Oxford, Sir William Dunn Sch Pathol, Oxford, England Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Infect Dis, Sch Med, Shanghai, Peoples R China Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China Shanghai Key Lab Emergency Prevent Diag & Treatme, Shanghai, Peoples R China |
| Keywords | ENTERICA SEROVAR TYPHIMURIUM PROTEIN POSTTRANSLATIONAL MODIFICATIONS ARGININE METHYLATION ESCHERICHIA-COLI SECRETION SYSTEM MOLECULAR CHARACTERIZATION BACTERIAL VIRULENCE TOLERANCE RESPONSE CHEMOTAXIS GENE |
| Issue Date | Sep-2021 |
| Publisher | MBIO |
| Abstract | 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. IMPORTANCE Posttranslational modifications (PTMs) play an important role in regulating enzyme activities, protein-protein interactions, or DNA-protein recognition and, consequently, modulate many biological functions. We demonstrated that PhoP, the response regulator of PhoP/PhoQ two-component system, could be methylated on several evolutionally conserved amino acid residues. These amino acid residues were crucial for PhoP phosphorylation or dimerization, DNA-binding ability of PhoP, and Salmonella virulence. Interestingly, methylation negatively regulated the activity of PhoP. A bacterial chemotaxis methyltransferase CheR was involved in PhoP methylation. Methylation of PhoP could stabilize it in an inactive conformation. Our work provides a more informative depiction of PhoP PTM and markedly improves our understanding of the coordinate regulation of bacterial chemotaxis and virulence. |
| URI | http://hdl.handle.net/20.500.11897/636967 |
| ISSN | 2150-7511 |
| DOI | 10.1128/mBio.02099-21 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
