Acetylation Regulating Protein Stability and DNA-Binding Ability of HilD, thus Modulating Salmonella Typhimurium Virulence.
HilD, a dominant regulator of Salmonella pathogenicity island 1, can be acetylated by protein acetyltransferase (Pat) in Salmonella Typhimurium, and the acetylation is beneficial to its stability. However, the underlying mechanism of HilD stability regulated by acetylation is not clear. We show here that lysine 297 (K297) located in the helix-turn-helix motif, can be acetylated by Pat. Acetylation of K297 increases HilD stability, but reduces its DNA-binding affinity. In turn, the deacetylated K297 enhances the DNA-binding ability but decreases HilD stability. Under the Salmonella pathogenicity island 1-inducing condition, the acetylation level of K297 is down-regulated. The acetylated K297 (mimicked by glutamine substitution) causes attenuated invasion in HeLa cells, as well as impaired virulence in mouse model, compared with the deacetylated K297 (mimicked by arginine substitution), suggesting that deacetylation of K297 is essential for Salmonella virulence. These findings demonstrate that the acetylation of K297 can regulate both protein stability and DNA-binding ability. This regulation mediated by acetylation not only degrades redundant HilD to keep a moderate protein level to facilitate S. Typhimurium growth but also maintains an appropriate DNA-binding activity of HilD to ensure bacterial pathogenicity.
Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
Yu
Y
Sang
Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
Jie
J
Ren
Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University.
Ran
R
Qin
Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
Shuting
S
Liu
Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University.
Zhongli
Z
Cui
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Sen
S
Cheng
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Xiaoyun
X
Liu
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.
Jie
J
Lu
Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.
Jing
J
Tao
Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences.|Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine.
Yu-Feng
YF
Yao
D000107:Acetylation; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; C119660:HilD protein, Salmonella typhimurium; D014157:Transcription Factors
DNA-binding; HilD; lysine acetylation; stability; virulence