In Vitro Resistance against DNA Gyrase Inhibitor SPR719 in Mycobacterium avium and Mycobacterium abscessus.

ABSTRACT: The aminobenzimidazole SPR719 targets DNA gyrase in Mycobacterium tuberculosis. The molecule acts as inhibitor of the enzyme's ATPase located on the Gyrase B subunit of the tetrameric Gyrase A₂B₂ protein. SPR719 is also active against non-tuberculous mycobacteria (NTM) and recently entered clinical development for lung disease caused by these bacteria. Resistance against SPR719 in NTM has not been characterized. Here, we determined spontaneous in vitro resistance frequencies in single step resistance development studies, MICs of resistant strains, and resistance associated DNA sequence polymorphisms in two major NTM pathogens Mycobacterium avium and Mycobacterium abscessus. A low-frequency resistance (10^-8/CFU) was associated with missense mutations

SUBMITTER: Aragaw WW 

PROVIDER: S-EPMC8754139 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature