Harnessing host-pathogen interactions for innovative drug discovery and host-directed therapeutics to tackle tuberculosis

Abstract

Tuberculosis (TB) is a highly contagious bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been ranked as the second leading cause of death worldwide from a single infectious agent. As an intracellular pathogen, Mtb has well adapted to the phagocytic host microenvironment, influencing diverse host processes such as gene expression, trafficking, metabolism, and signaling pathways of the host to its advantage. These responses are the result of dynamic interactions of the bacteria with the host cell signaling pathways, whereby the bacteria attenuate the host cellular processes for their survival. Specific host genes and the mechanisms involved in the entry and subsequent stabilization of M. tuberculosis intracellularly have been identified in various genetic and chemical screens recently. The present understanding of the co-evolution of Mtb and macrophage system presented us the new possibilities for exploring host-directed therapeutics (HDT). Here, we discuss the host-pathogen interaction for Mtb, including the pathways adapted by Mtb to escape immunity. The review sheds light on different host-directed therapies (HDTs) such as repurposed drugs and vitamins, along with their targets such as granuloma, autophagy, extracellular matrix, lipids, and cytokines, among others. The article also examines the available clinical data on these drug molecules. In conclusion, the review presents a perspective on the current knowledge in the field of HDTs and the need for additional research to overcome the challenges associated HDTs.