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, et al. (12 authors)
Antimicrobial Agents and Chemotherapy · 2021-10
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.
MeSH terms
- DNA gyrase
- Mycobacterium abscessus
- Mycobacterium tuberculosis
- Microbiology
- Nontuberculous mycobacteria
- Topoisomerase IV
- Drug resistance
- Mycobacterium
- Tuberculosis
- Mycobacterium bovis
- Topoisomerase
- Antibacterial agent
- Biology
- DNA
- Mycobacterium smegmatis
- Ofloxacin
- Mutant
- Antibiotics