Targeting Autophagy as a Strategy for Developing New Host-Directed Therapeutics Against Nontuberculous Mycobacteria

Nontuberculous mycobacteria (NTMs) are increasingly being recognized as opportunistic pathogens in clinical practice because of their innate resistance to antimicrobial treatment and the widespread increase in multidrug-resistant strains on a global scale. NTMs pose a tremendous infection management challenge, especially in individuals with pre-existing lung conditions, as well as those who are immunocompromised. NTMs' capability to evade or suppress the immune responses of their host is a key feature that makes them a cause of persistent chronic infection. Autophagy, an essential cellular defense mechanism that delivers and breaks down intracellular materials in lysosomes, protects the host from mycobacterial infection. Initial studies have revealed encouraging therapeutic strategies that augment endogenous autophagic mechanisms or block harmful host responses, thus having the potential to decrease intracellular mycobacterial infection, including that caused by multidrug-resistant strains. This review discusses how NTMs can evade autophagic mechanisms and considers the possibilities of using autophagy-inducing agents to develop novel therapeutic strategies to combat NTM infection.