Therapeutic potential of promiscuous targets in Mycobacterium tuberculosis

In the field of tuberculosis drug development, the term `promiscuous' was coined to collectively describe targets that repeatedly show up in whole-cell screenings. With the current climate leaning towards the exclusion of these targets in future drug screens, this review discusses and clarifies misconceptions surrounding this classification, the prospects of developing compounds targeting promiscuous targets, and their potential impact on tuberculosis drug development. The dominance of these targets in cell-based screens reflect not only bias introduced by experimental setup, but also some of the pathogen's greatest vulnerabilities. Coupled with favourable predictions of their in vivo efficacies and synergism with other TB drugs, these targets open opportunities to be explored for the development of rational drug combination for tuberculosis.