Chemical tools for illumination of tuberculosis biology, virulence mechanisms, and diagnosis

Abstract

Tuberculosis (TB) remains one of the deadliest infectious diseases and begs the scientific community to up the ante for research and exploration of completely novel therapeutic avenues. Chemical biology-inspired design of tunable chemical tools has aided in clinical diagnosis, facilitated discovery of therapeutics, and begun to enable investigation of virulence mechanisms at the host–pathogen interface of Mycobacterium tuberculosis. This Perspective highlights chemical tools specific to mycobacterial proteins and the cell lipid envelope that have furnished rapid and selective diagnostic strategies and provided unprecedented insights into the function of the mycobacterial proteome and lipidome. We discuss chemical tools that have enabled elucidating otherwise intractable biological processes by leveraging the unique lipid and metabolite repertoire of mycobacterial species. Some of these probes represent exciting starting points with the potential to illuminate poorly understood aspects of mycobacterial pathogenesis, particularly the host membrane–pathogen interactions.