Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global health threat, worsened by the emergence of drug-resistant strains and by the lengthy six-month treatment time needed to effectively manage the disease. The drug bedaquiline (BDQ) is now a key component of novel regimens for treating multi-drug resistant (MDR) tuberculosis, but its effectiveness is threatened by newer drug-resistant Mtb strains.

William R. Jacobs Jr., Ph.D., and Catherine Vilcheze, Ph.D., have recently investigated whether vitamin C could enhance BDQ’s activity against Mtb. The researchers found that combining BDQ with vitamin C eliminated drug-susceptible as well as multi-drug-resistant Mtb cultures in vitro within 21 days. The combination also enhanced Mtb killing in infected human macrophages and peripheral blood mononuclear cells. Further analysis revealed that the BDQ/vitamin C combination induces widespread metabolic disruption in Mtb, characterized by upregulation of stress response, metal ion homeostasis genes and downregulation of energy metabolism and cell-wall biosynthesis genes. The findings suggest that vitamin C could be a safe and inexpensive adjunct that enhances the effectiveness of the current TB drug regimen, shortens treatment times, and counteracts drug resistance during treatment for multi-drug-resistant TB.

The results were published online on June 25 in mBio. Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology and professor of genetics and of microbiology & immunology at Einstein. Dr. Vilcheze, a research assistant professor in microbiology & immunology at Einstein is the first author on the study.