Professor Nicolas Willand's team (M2SV, Drug Discovery Center) has invented a new chemical family of Mycobacterium tuberculosis Gyrase inhibitors whose activity and mode of action have been characterized at the atomic level in collaboration with Dr. Stéphanie Petrella's team.
Antimicrobial resistance remains a major public health problem at a time when the therapeutic arsenal tends to dwindle. In an article published in the journal iScience, researchers from the Drug Discovery Center of the Pasteur Institute of Lille They describe the discovery of novel inhibitors targeting DNA gyrase, a well-validated drug target for the development of new antibiotics. These compounds exhibit potent antibacterial activity against various pathogenic bacteria, including Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis.
Furthermore, the molecule, called BDM71403, proved more potent against the bacteria than the currently marketed reference compound, gepotidacin. High-resolution cryo-electron microscopy structural analysis, conducted in collaboration with Dr. Stéphanie Petrella's team, the Pasteur Institute of ParisThis study has provided detailed information on the ternary complex formed by Mtb gyrase, double-stranded DNA, and BDM71403. It highlights the potential of these derivatives containing this triazole motif as promising gyrase inhibitors, thus offering new avenues for developing novel drugs to combat antimicrobial resistance.
This scientific collaboration illustrates the strength of the Pasteur Network, an international network of Pasteur Institutes, where each member (33 in 2024), although independent of each other, collaborate and exchange to advance health and the understanding of living things.
