ReviewGene-to-screenIdentification and validation of novel drug targets in Mycobacterium tuberculosis

- Prodrugs are over-represented among hits from phenotypic screens.
- Hypomorphs are versatile tools for use in TB drug target validation.
- Innovative screens hold promise for identifying antituberculars with novel MOA.

Tuberculosis (TB) is a global epidemic associated increasingly with resistance to first- and second-line antitubercular drugs. The magnitude of this global health threat underscores the urgent need to discover new antimycobacterial agents that have novel mechanisms of action (MOA). In this review, we highlight some of the key advances that have enabled the strengths of target-led and phenotypic approaches to TB drug discovery to be harnessed both independently and in combination. Critically, these promise to fuel the front-end of the TB drug pipeline with new, pharmacologically validated drug targets together with lead compounds that act on these targets.