Abstract
Mycobacterial disease is an immense burden worldwide. This disease group includes tuberculosis, leprosy (Hansen’s disease), Buruli Ulcer, and non-tuberculous mycobacterial (NTM) disease. The burden of NTM disease, both pulmonary and ulcerative, is drastically escalating globally, especially in developed countries such as America and Australia. Mycobacteria’s ability to inhibit or evade the host immune system has contributed significantly to its continued prevalence. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. Autophagy is a cell-autonomous host defense mechanism by which intracytoplasmic cargos can be delivered and then destroyed in lysosomes. Previous studies have reported that autophagy-activating agents, small molecules, and autophagy-activating vaccines may be beneficial in restricting intracellular mycobacterial infection, even with multidrug-resistant strains. This review will examine how mycobacteria evade autophagy and discusses how autophagy could be exploited to design novel TB treatment strategies, such as host-directed therapeutics and vaccines, against Mycobacterium tuberculosis and NTMs.
Highlights
While TB is a disease of significant global burden, the burden of non-tuberculosis mycobacteria (NTM) disease is higher than TB in many developed countries such as the United States and Australia (Prevots et al, 2010)
The NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs and the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides
It has previously been shown that treatment of Mycobacterium tuberculosis (Mtb) infected macrophages with potent autophagy inducers such as M. smegmatis can clear bacteria (Singh et al, 2017)
Summary
While TB is a disease of significant global burden, the burden of non-tuberculosis mycobacteria (NTM) disease is higher than TB in many developed countries such as the United States and Australia (Prevots et al, 2010). Mtb inhibits autophagy to protect against bacterial clearance and host cell death, which impedes antigen presentation. There may be value in examining host-directed therapies targeting mTOR-independent autophagy pathways (Schiebler et al, 2015), since Mtb infection markedly activates mTOR.
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