A Mycobacterium tuberculosis NBTI DNA Gyrase Inhibitor Is Active against Mycobacterium abscessus
Uday S. Ganapathy, Rubén González del Río, Mónica Cacho-Izquierdo, Fátima Ortega, Joël Lelièvre, David Barros-Aguirre, Wassihun Wedajo Aragaw, Matthew D. Zimmerman, Marissa Lindman, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Abstract
. Focusing on M. abscessus, which causes the most difficult to cure NTM disease, we show that EC/11716 is bactericidal, active against drug-tolerant biofilms, and efficacious in a murine model of M. abscessus lung infection. Based on resistant mutant selection experiments, we report a low frequency of resistance to EC/11716 and confirm DNA gyrase as its target. Our findings demonstrate the potential of NBTIs as anti-M. abscessus and possibly broad-spectrum anti-mycobacterial agents.
Topics & Concepts
DNA gyraseMycobacterium abscessusMycobacterium tuberculosisMicrobiologyNontuberculous mycobacteriaTopoisomerase IVDrug resistanceMycobacteriumTuberculosisMycobacterium bovisTopoisomeraseAntibacterial agentBiologyDNAMycobacterium smegmatisOfloxacinMutantAntibioticsMedicineIsoniazidDrugVirologyCancer therapeutics and mechanismsTuberculosis Research and EpidemiologySynthesis and biological activity