Adding to the arsenal: targeting human proteins for controlling M. tuberculosis growth
The National Institute of Health envisions a plan for managing tuberculosis in the 21st century. Included in this proposal is targeting host proteins as an add-on therapy to antibiotics. Infectious disease biologists are focusing on this strategy and it is a topic of active research. Recently, a multinational research team identified a macrophage-resident host protein that is utilised by Mycobacterium tuberculosis for its survival. This discovery adds to the expanding list of host proteins that can be targeted with existing drugs. In this article, Navodita Jain discusses the importance of this novel target and how these studies provide an impetus to drug repurposing for treating infectious diseases.
TUBERCULOSIS (TB) infected about 10 million people globally and claimed about 1.2 million lives in 2018. The global health burden of the disease is complicated by a significant population harbouring latent infection and/or affected by the multidrug resistant strain. One of the major challenges with TB treatment is patients failing to adhere to the prolonged treatment course which spans about six to nine months. Therapy also has largely been antibacterial and has not been modified in about 40 years.
Recently, scientists at the Borstel-Leibniz Lung Center, Germany, and the Indian Institute of Technology Indore discovered1 that a human channel protein is utilised by Mycobacterium tuberculosis (Mtb) for its survival. The protein causes nutrient enrichment within Mtb-infected macrophages and helps Mtb evade immune surveillance by decreasing cytokine signalling. This discovery provides an opportunity to modulate host proteins to restrict pathogen survival. Interestingly, drugs against the said host protein have been under development for other disease areas and could work as an add-on therapy. The adjunct therapy could potentially lead to treatment duration reduction and a faster culture-negative TB.
Borstel-Leibniz Lung Center, Fluidic Analytics, GlaxoSmithKline (GSK), Indian Institute of Technology, John Hopkins University, The Aurum Institute, US National Institute of Allergy and Infectious Diseases (NIAID)