Acetylation of Lysine 201 Inhibits the DNA-Binding Ability of PhoP to Regulate Salmonella Virulence

PLoS Pathogens

Jie Lu¹  Wenjuan Wu²  Yu Sang³  Yu-Feng Yao³  Xia Fan³  Wei Zhao³  Jie Ren³  Jinjing Ni³  Yongcong Tan³  Jing Tao³  Shuting Liu³ 

[1] Department of Infectious Diseases, Shanghai Ruijin Hospital, Shanghai, China;Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China

关键词: Acetylation;    Salmonella typhimurium;    Macrophages;    Immunoprecipitation;    Deletion mutagenesis;    Lysine;    Mouse models;    DNA transcription;   

DOI  :  10.1371/journal.ppat.1005458

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The two-component system PhoP-PhoQ is highly conserved in bacteria and regulates virulence in response to various signals for bacteria within the mammalian host. Here, we demonstrate that PhoP could be acetylated by Pat and deacetylated by deacetylase CobB enzymatically in vitro and in vivo in Salmonella Typhimurium. Specifically, the conserved lysine residue 201(K201) in winged helix–turn–helix motif at C-terminal DNA-binding domain of PhoP could be acetylated, and its acetylation level decreases dramatically when bacteria encounter low magnesium, acid stress or phagocytosis of macrophages. PhoP has a decreased acetylation and increased DNA-binding ability in the deletion mutant of pat. However, acetylation of K201 does not counteract PhoP phosphorylation, which is essential for PhoP activity. In addition, acetylation of K201 (mimicked by glutamine substitute) in S. Typhimurium causes significantly attenuated intestinal inflammation as well as systemic infection in mouse model, suggesting that deacetylation of PhoP K201 is essential for Salmonella pathogenesis. Therefore, we propose that the reversible acetylation of PhoP K201 may ensure Salmonella promptly respond to different stresses in host cells. These findings suggest that reversible lysine acetylation in the DNA-binding domain, as a novel regulatory mechanism of gene expression, is involved in bacterial virulence across microorganisms.

【 授权许可】

CC BY