Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation

  • Emerg Microbes Infect. 2019;8(1):55-69. doi: 10.1080/22221751.2018.1558963.
Jie Ren  1 ,  Yu Sang  1 ,  Ran Qin  2 ,  Yang Su  1 ,  Zhongli Cui  2 ,  Zhiguo Mang  3 ,  Hao Li  3 ,  Shaoyong Lu  4 ,  Jian Zhang  4 ,  Sen Cheng  5 ,  Xiaoyun Liu  5 ,  Jixi Li  6 ,  Jie Lu  7 ,  Wenjuan Wu  8 ,  Guo-Ping Zhao  9 ,  Feng Shao  10 ,  Yu-Feng Yao  1  8
Affiliations
  • 1. a Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology , Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine , Shanghai , People's Republic of China.
  • 2. b Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture , College of Life Sciences, Nanjing Agricultural University , Nanjing , People's Republic of China.
  • 3. c Department of Pharmaceutical Science , School of Pharmacy, East China University of Science & Technology , Shanghai , People's Republic of China.
  • 4. d Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , People's Republic of China.
  • 5. e Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center , College of Chemistry and Molecular Engineering, Peking University , Beijing , People's Republic of China.
  • 6. f State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Engineering Research Center of Industrial Microorganisms , School of Life Sciences, Fudan University , Shanghai , People's Republic of China.
  • 7. g Department of Infectious Diseases , Shanghai Ruijin Hospital , Shanghai , People's Republic of China.
  • 8. h Department of Laboratory Medicine , Shanghai East Hospital, Tongji University School of Medicine , Shanghai , People's Republic of China.
  • 9. i Key Laboratory of Synthetic Biology , Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai , People's Republic of China.
  • 10. j National Institute of Biological Sciences , Beijing , People's Republic of China.
PMID: 30866760 DOI: 10.1080/22221751.2018.1558963
Abstract

Accumulating 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.

Keywords
Acetyl phosphate; PhoP; acetylation; metabolism; phosphorylation; virulence.
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