Autophagy as a Target for Host-Directed Therapy Against Tuberculosis

Abstract

Autophagy is the cellular self-degradative process crucial for the maintenance of homeostasis. Recent developments in the field highlight its importance in the control of several pathogens ranging from bacteria to viruses leading to its emergence as the potential host directed therapeutic pathway of choice for pathogenic infections. Taking cues from its role in shaping the outcome of Mycobacterium tuberculosis (Mtb) infection, which is the causative agent of the deadliest disease known to humanity, tuberculosis (TB), several anti-TB therapies have been envisioned based on manipulation of autophagy. Recent advances in understanding the regulation of autophagy, especially during Mtb infection, has unraveled diverse potential ways to target the pathogen through autophagy which includes features like mTOR dependent and independent autophagy, role of protein kinase activators, AMPK and SIRT regulators etc. At the same time, role of diverse bacterial virulence factors in altering the host autophagy responses has also emerged. In this chapter, we discuss the interplay of host and Mtb, spotlighting the major factors involved in autophagy-dependent targeting of the pathogen and explore the prospects for future host-directed anti-TB therapeutics.