Metformin as a potential combination therapy with existing front-line antibiotics for Tuberculosis

Abstract

Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) remains a global health concern. The evolution of various multi-drug resistant strains through genetic mutations or drug tolerant strains through bacterial persistence renders existing antibiotics ineffective. Hence there is need for the development of either new antibiotics or rationalizing approved drugs that can be utilized in combination with existing antibiotics as a therapeutic strategy. A comprehensive systems level mapping of metabolic complexity in Mtb revels a putative role of NDH-I in the formation of bacterial persistence under the influence of front-line antibiotics. Possibilities of targeting bacterial NDH-I with existing FDA approved drug for type-II diabetes, Metformin, along with existing front-line antibiotics is discussed and proposed as a potential combination therapy for TB.

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Figure 1

Metformin, an FDA approved drug for type-II diabetes as a potential combination therapy for Tuberculosis with existing antibiotics. a) Antibiotic targeting mycolic acid biosynthesis; b) systems-level changes resulting into the reduction of flux carrying capacity of glycolysis and citric acid cycle c) resulting re-routing of metabolic fluxes through de novo NAD biosynthesis pathway and electron transport through NDH-I d) possibility of targeting NDH-I with metformin.