Metformin as adjunct antituberculosis therapy

Metformin can be repurposed as host-directed therapy for tuberculosis. Diabetes Drug Treats TB The increasing prevalence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) has led to a paradigm shift in the search for new drugs. Rather than targeting the bacterium, researchers are trying to augment the host response. Now, Singhal et al. report that the FDA-approved drug metformin, which is currently used to treat type 2 diabetes, can improve the immune response to Mtb infection. They show in vitro and in vivo in Mtb-infected mice that metformin can control the growth of Mtb by enhancing the specific immune response. Indeed, in human diabetic patients infected with Mtb, metformin treatment was associated with improved control and decreased disease severity. These data suggest that metformin could be used as adjuvant therapy to treat Mtb infection. The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is to augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate–activated protein kinase)–dependent manner. MET controls the growth of drug-resistant Mtb strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. In Mtb-infected mice, use of MET ameliorated lung pathology, reduced chronic inflammation, and enhanced the specific immune response and the efficacy of conventional TB drugs. Moreover, in two separate human cohorts, MET treatment was associated with improved control of Mtb infection and decreased disease severity. Collectively, these data indicate that MET is a promising candidate host-adjunctive therapy for improving the effective treatment of TB.