The high acquisition of drug resistance by Mycobacterium tuberculosis necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high throughput screening of compounds against thiol-deficient M. smegmatis strains and subsequent validations with thiol-deficient M. tuberculosis strains, revealed that egtA and mshA mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su), egtB and egtE mutants had increased susceptibility to bacitracin (Ba) and egtA, mshA, and egtB mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the level of thiols and oxidative stress in M. tuberculosis. This study indicates the activity of Aza, Su, Fu and Ba against M. tuberculosis and provide a rationale for further investigations.
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