Antimicrobial Agents and Chemotherapy · 2018 · 19 citations · 69 references
MedicineMedicinal ChemistryPharmacologyAntimicrobial PharmacologyChemotherapyDrug DiscoveryAntibiotic ResistanceAntimicrobial Susceptibility TestingPulmonary TuberculosisTuberculosis PharmacotherapyAnti-tuberculosis Drug RepurposingHigh-throughput Screening AssaysMycobacterium Tuberculosis InfectionMycobacterium Tuberculosis PathogenesisPhenotypic Drug Susceptibility TestingRate Of AcquisitionTuberculosis Drug DevelopmentTuberculosis Drug Resistance
ABSTRACT The high acquisition rate 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 Mycobacterium smegmatis strains and subsequent validation with thiol-deficient M. tuberculosis strains revealed that ΔegtA and ΔmshA mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); ΔegtB and ΔegtE mutants had increased susceptibility to bacitracin (Ba); and ΔegtA , ΔmshA , and ΔegtB 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 M. tuberculosis . This study reports the activities of Aza, Su, Fu, and Ba against M. tuberculosis and provides a rationale for further investigations.
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