Compounds with Potential Activity against Mycobacterium tuberculosis

Abstract

The high acquisition rate of drug resistance by <i>Mycobacterium tuberculosis</i> 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 <i>Mycobacterium smegmatis</i> strains and subsequent validation with thiol-deficient <i>M. tuberculosis</i> strains revealed that <i>ΔegtA</i> and <i>ΔmshA</i> mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); <i>ΔegtB</i> and <i>ΔegtE</i> mutants had increased susceptibility to bacitracin (Ba); and <i>ΔegtA</i>, <i>ΔmshA</i>, and <i>ΔegtB</i> 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 in <i>M. tuberculosis</i> This study reports the activities of Aza, Su, Fu, and Ba against <i>M. tuberculosis</i> and provides a rationale for further investigations.