Harnessing the mTOR Pathway for Tuberculosis Treatment

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Tuberculosis (TB) is a major infectious disease globally, treated with multi-drug regimens for at least six months.
• Current treatments face challenges including patient non-compliance and the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb).
• Host-intrinsic factors and Mtb's manipulation of host immunity contribute to treatment failure and drug resistance.

Purpose of the Study:

• To review the role of autophagy in Mtb pathogenesis.
• To explore the mechanistic target of rapamycin (mTOR) pathway in Mtb infection.
• To evaluate the potential of modulating the mTOR pathway as a host-directed therapeutic (HDT) strategy for TB.

Main Methods:

• Literature review on autophagy, mTOR signaling, and host-directed therapies in tuberculosis.
• Analysis of Mtb's interaction with host cellular processes, particularly autophagy.
• Examination of mTOR pathway inhibitors as adjunctive treatments for TB.

Main Results:

• Autophagy plays a critical role in cellular defense against Mtb, but Mtb can subvert this process.
• The mTOR pathway is a key regulator of autophagy and cellular responses to Mtb.
• Modulating the mTOR pathway presents a viable strategy for enhancing host immunity against Mtb.

Conclusions:

• Host-directed therapeutics (HDT) targeting cellular processes like autophagy offer a novel approach to combat TB.
• Modulating the mTOR pathway with inhibitors, in conjunction with standard antibiotics, may improve TB treatment outcomes.
• HDT strategies hold potential for reducing treatment duration and overcoming drug resistance in TB.