Compounds with Potential Activity against Mycobacterium tuberculosis

The high acquisition rate of drug resistance byMycobacterium 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-deficientMycobacterium smegmatis strains and subsequent validation with thiol-deficientM. tuberculosis strains revealed thatΔegtA andΔmshA mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su);ΔegtB andΔegtE mutants had increased susceptibility to bacitracin (Ba); andΔegtA ,ΔmshA , andΔegtB mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress inM. tuberculosis . This study reports the activities of Aza, Su, Fu, and Ba againstM. tuberculosis and provides a rationale for further investigations.