Abstract
Tuberculosis, especially multidrug resistant cases, remains an enormous public health threat. Mycobacterium tuberculosis metC (Rv3340) an enzyme involved in methionine biosynthesis was identified and characterised for antimicrobial susceptibility. We reported that the overexpression of Rv3340 in Mycobacterium smegmatis (Ms_Rv3340) produces hydrogen sulphide (H
2
S) for its energy in harsh conditions. The produced H
2
S sustained Ms_Rv3340 against streptomycin, whereas the chemical inhibition of H
2
S caused streptomycin lethality to Ms_Rv3340. Further analysis showed that cysteine-H
2
O
2
treatment of Ms-Rv3340 initiated DNA damage via Fenton reaction. Ms_Rv3340 downregulated the expression levels of three streptomycin responsive genes. To our knowledge, no study has been previously reported that M. tuberculosis metC (Rv3340) can generates H
2
S modulating resistant to streptomycin which provides a greater perception toward the treatment and control of tuberculosis.