The Structural Features of Novel Bacterial Topoisomerase InhibitorsThat Define Their Activity on Topoisomerase IV

The continued emergence of bacterial resistancehas created an urgent need for new and effective antibacterialagents. Bacterial type II topoisomerases, such as DNA gyrase andtopoisomerase IV (topoIV), are well-validated targets forantibacterial chemotherapy. The novel bacterial topoisomeraseinhibitors (NBTIs) represent one of the new promising classes ofantibacterial agents. They can inhibit both of these bacterialtargets; however, their potencies differ on the targets amongspecies, making topoIV probably a primary target of NBTIs inGram-negative bacteria. Therefore, it is important to gain aninsight into the NBTIs key structural features that govern thetopoIV inhibition. However, in Gram-positive bacteria, topoIV isalso a significant target for achieving dual-targeting, which in turn contributes to avoiding bacterial resistance caused by single-targetmutations. In this perspective, we address the structure-activity relationship guidelines for NBTIs that target the topoIV enzyme inGram-positive and Gram-negative bacteria.

Automated summary

The emergence of bacterial resistance has created a need for new and effective antibacterial agents. Novel bacterial topoisomerase inhibitors (NBTIs) represent a promising class of antibacterial agents that can target different bacterial species with varying potencies.