The ΔCysK2 mutant of Mycobacterium tuberculosis is sensitive to vancomycin associated with changes in cell wall phospholipid profile

Biochem Biophys Res Commun. 2022 Oct 8:624:120-126. doi: 10.1016/j.bbrc.2022.07.096. Epub 2022 Aug 2.

Abstract

Cysteine plays a versatile role in cellular physiology and has previously been shown to be instrumental to Mycobacterium tuberculosis (M.tb) pathophysiology. In this study, we have generated mutants deficient in CysK2 and CysH, the key Cysteine, biosynthetic enzymes. In contrast to the ΔcysH mutant, the ΔcysK2 mutant is not an auxotroph and as such not essential for cysteine biosynthesis. Interestingly, the ΔcysK2 mutant shows increased sensitivity to cumene hydroperoxide, vitamin C, diamide, rifampicin and Vancomycin and shows alterations in phospholipid profile of Mtb cell wall. Our findings suggest that alteration in phospholipids content of M.tb cell wall by CysK2 may form a mode of defence against selected antibiotics and oxidative stress.

Keywords: CysK(2); Cysteine; Mycobacterium tuberculosis; Oxidative stress; Phospholipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall
  • Cysteine / genetics
  • Mycobacterium tuberculosis* / genetics
  • Phospholipids
  • Vancomycin / pharmacology

Substances

  • Phospholipids
  • Vancomycin
  • Cysteine