Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is a fatal infectious disease that prevails to be the second leading cause of death from a single infectious agent despite the availability of multiple drugs for treatment. The current treatment regimen involves the combination of several drugs for 6 months that remain ineffective in completely eradicating the infection because of several drawbacks, such as the long duration of treatment and the side effects of drugs causing non-adherence of patients to the treatment regimen. Autophagy is an intracellular degradative process that eliminates pathogens at the early stages of infection. Mycobacterium tuberculosis's unique autophagy-blocking capability makes it challenging to eliminate compared to usual pathogens. The present review discusses recent advances in autophagy-inhibiting factors and mechanisms that could be exploited to identify autophagy-inducing chemotherapeutics that could be used as adjunctive therapy with the existing first-line anti-TB agent to shorten the duration of therapy and enhance cure rates from multidrug-resistant tuberculosis (MDR-TB) and extreme drug-resistant tuberculosis (XDR-TB).

Keywords: Autophagy; Host cell inhibitors; Host defense; Tuberculosis.