Inhibiting respiration as a novel antibiotic strategy

The approval of the first-in-class antibacterial bedaquiline for tuberculosis marks a breakthrough in antituberculosis drug development. The drug inhibits mycobacterial respiration and represents the validation of a wholly different metabolic process as a druggable target space. In this review, we d...

Full description

Saved in:
Bibliographic Details
Main Authors: Lee, Bei Shi, Singh, Samsher, Pethe, Kevin
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10356/170915
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
Description
Summary:The approval of the first-in-class antibacterial bedaquiline for tuberculosis marks a breakthrough in antituberculosis drug development. The drug inhibits mycobacterial respiration and represents the validation of a wholly different metabolic process as a druggable target space. In this review, we discuss the advances in the development of mycobacterial respiratory inhibitors, as well as the potential of applying this strategy to other pathogens. The non-fermentative nature of mycobacteria explains their vulnerability to respiration inhibition, and we caution that this strategy may not be equally effective in other organisms. Conversely, we also showcase fundamental studies that reveal ancillary functions of the respiratory pathway, which are crucial to some pathogens' virulence, drug susceptibility and fitness, introducing another perspective of targeting bacterial respiration as an antibiotic strategy.