Metformin and Rifampicin combination augments active to latent tuberculosis conversion: A computational study

Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR-DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.