Regulation of ergothioneine biosynthesis and its effect on Mycobacterium tuberculosis growth and infectivity

Academic Article

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 . 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 nutrientstarved model of persistence and is needed for long term infection of murine macrophages. 213
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    Author List

  • Richard-Greenblatt M; Bach H; Adamson J; Peña-Diaz S; Li W; Steyn AJC; Av-Gay Y
  • Start Page

  • 23064
  • End Page

  • 23076
  • Volume

  • 290
  • Issue

  • 38