Weak Links: Advancing Target-Based Drug Discovery by Identifying the Most Vulnerable Targets

Mycobacterium tuberculosis remains the most common infectious killer worldwide despite decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) pandemic will require innovation in drug discovery. In this review, we provide a brief overview of the two main approaches to discovering new TB drugs-phenotypic screens and target-based drug discovery-and outline some of the limitations of each method. We then explore recent advances in genetic tools that aim to overcome some of these limitations. In particular, we highlight a novel metric to prioritize essential targets, termed vulnerability. Stratifying targets based on their vulnerability presents new opportunities for future target-based drug discovery campaigns. Mycobacterium tuberculosis (TB) is the leading cause of death due to infectious disease. Developing new antibiotics that can shorten TB treatment time will require innovation in target-based drug discovery in addition to phenotypic screens. In this review, we highlight a novel metric to prioritize essential targets: vulnerability. Stratifying targets based on their vulnerability, in addition to more traditional target prioritization metrics, presents new opportunities for future target-based drug discovery campaigns. image