DNA topoisomerase I and DNA gyrase as targets for TB therapy

•DNA topoisomerases are key targets for antibacterial and anticancer chemotherapy.•TB topo I is validated as an antibacterial target.•Inhibitors that target TB topo I have been found.•Gyrase is already successful as a TB target (e.g. fluoroquinolones).•Further gyrase-targeting agents can be developed.

Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy. Here, we review the exploitation of topoisomerases as antibacterial targets and summarize progress in developing new agents to target DNA topoisomerase I and DNA gyrase from Mycobacterium tuberculosis.