Insights into Novel Drug Targets in Mycobacterium tuberculosis: Where Do We Stand and Where Do We Go from Here?

Abstract

Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS with 6.3 million new cases of TB reported in 2016. TB is an air-borne disease associated with the aerobic bacterium Mycobacterium tuberculosis (Mtb), which mainly infects the lungs. Aerosolization of diseased pulmonary secretions, by coughing, sneezing and speaking, discharge the Mtb bacilli into the atmosphere. Infected aerosol droplet nuclei sized 1-10 μm are largely trapped in the upper nasal passages or are expelled into the pharynx by the mucociliary mechanism of the lower respiratory tract and are harmlessly swallowed and digested. Infected persons may overcome the initial TB infection, resulting in the development of asymptomatic latent TB. About 10% of individuals may develop the active disease after infection; where the bacteria undergo more rapid growth and overcome the host immune system. In cases of multi-drug resistant (MDR) strains, and extreme drug-resistant (XDR) strains, treatment fails, and the bacteria propagate and attack the host, leading to death from systemic infection. Due to the increased spread of TB worldwide, both the academic and industrial communities have initiated intensive research to develop new therapeutics targeting new enzymes such as cytochrome P450s in Mtb.