| Tuberculosis,especially multidrug resistant cases,remains an enormous public health threat.Hydrogen sulfide?H2S?is currently emerging as a vital gaseous mediator in the pathophysiology of Mycobacterium tuberculosis.Mycobacterium tuberculosis Rv3340?metC?gene penultimate step in methionine biosynthesis by breakdown cystathionine into homocysteine.We cloned and expressed Mycobacterium tuberculosis Rv3340?metC?in Mycobacterium smegmatis then treated under the presence of cysteine,sulfate,antibiotics and NaHS as a sole sulfur source either in normoxia or hypoxia.We reported that the overexpression of Rv3340 in Mycobacterium smegmatis?MsRv3340/MsmetC?induces hydrogen sulfide?H2S?for its energy in harsh conditions.We found that MsRv3340 diminished the potentiality to survive when in exposure to H2O2 and we suggested that MsRv3340 enhance resistance against streptomycin via H2S.The recombinant MsRv3340 initiated DNA damage via Fenton reaction and MsRv3340downregulated the expression levels of three streptomycin responsive genes.Within the limit of this study,our results showed that H2S enhanced the MsmetC in hypoxia.We found that recombinant MsmetC in the presence of sulfate stimulates cysteine excretion and cysteine enhances the rapid growth of MsmetC in normoxia.The pH curves indicate that MsmetC is pH-dependent on the presence of an H2S donor.MsmetC becomes sensitive in hypoxia under the presence of cysteine and MsmetC exposure to H2S donor enhance rapid growth,hence may be associated with H2S.To our knowledge,no study has been previously reported that Mycobacterium tuberculosis Rv3340?metC?can generates H2S and resistance to streptomycin.These findings implying that the MsmetC under various environments either normoxia or hypoxia induces H2S with different potential biological role benefits for recombinant MsmetC survival.We suggest that drug targeting H2S production may be potentially useful to control Mycobacterium tuberculosis. |
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