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J Biol Chem. 2015 Sep 18;290(38):23064-76. doi: 10.1074/jbc.M115.648642. Epub 2015 Jul 30.

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity.

Author information

  • 1From the Division of Infectious Diseases, Department of Medicine and.
  • 2Kwazulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa 4001.
  • 3Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
  • 4Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 400715, China, and.
  • 5Kwazulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa 4001, Department of Microbiology and Centers for AIDS Research and Free Radical Biology, University of Alabama, Birmingham, Alabama 35233.
  • 6From the Division of Infectious Diseases, Department of Medicine and yossi@mail.ubc.ca.

Abstract

Ergothioneine (EGT) is synthesized in mycobacteria, but limited knowledge exists regarding its synthesis, physiological role, and regulation. We have identified Rv3701c from Mycobacterium tuberculosis to encode for EgtD, a required histidine methyltransferase that catalyzes first biosynthesis step in EGT biosynthesis. EgtD was found to be phosphorylated by the serine/threonine protein kinase PknD. PknD phosphorylates EgtD both in vitro and in a cell-based system on Thr(213). The phosphomimetic (T213E) but not the phosphoablative (T213A) mutant of EgtD failed to restore EGT synthesis in a ΔegtD mutant. The findings together with observed elevated levels of EGT in a pknD transposon mutant during in vitro growth suggests that EgtD phosphorylation by PknD negatively regulates EGT biosynthesis. We further showed that EGT is required in a nutrient-starved model of persistence and is needed for long term infection of murine macrophages.

KEYWORDS:

Mycobacterium tuberculosis; bacterial protein kinase; bacterial signal transduction; ergothioneine; histidine methylation; microbiology; thiol

PMID:
26229105
PMCID:
PMC4645607
DOI:
10.1074/jbc.M115.648642
[PubMed - indexed for MEDLINE]
Free PMC Article
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