Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis

Significance Tuberculosis (TB) patients would greatly benefit from shorter treatment options. The treatment of drug-susceptible TB, a disease caused by the bacillus Mycobacterium tuberculosis , is a lengthy and strenuous process. This long therapy is because of the ability of a small population of cells to become drug-tolerant. Here, we demonstrate that the addition of small thiols to drug-treated M. tuberculosis prevents the emergence of drug-tolerant but also drug-resistant cells leading to sterilization of the cultures in vitro. The thiols potentiate drug activity by preventing the cells from entering a persister state and shutting down their metabolism while generating an oxidative burst. This dual mechanism of killing could lead to novel approaches to shorten TB chemotherapy.