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

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.