Amino acid 17 in QRDR of Gyrase A plays a key role in fluoroquinolones susceptibility in mycobacteria

Microbiol Spectr. 2023 Dec 12;11(6):e0280923. doi: 10.1128/spectrum.02809-23. Epub 2023 Oct 13.

Abstract

Fluoroquinolones (FQs) play a key role in the treatment regimens against tuberculosis and non-tuberculous mycobacterial infections. However, there are significant differences in the sensitivities of different mycobacteria to FQs. In this study, we proved that this is associated with the polymorphism at amino acid 17 of quinolone resistance-determining region of Gyrase A by gene editing. This is the first study using CRISPR-associated recombination for gene editing in Mycobacterium abscessus to underscore the contribution of the amino acid substitutions in GyrA to FQ susceptibilities in mycobacteria.

Keywords: Mycobacterium abscessus; fluoroquinolone; gene editing; intrinsic resistance; mycobacteria.

MeSH terms

  • Amino Acids
  • DNA Gyrase / genetics
  • Drug Resistance, Bacterial / genetics
  • Fluoroquinolones / pharmacology
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis* / genetics
  • Mycobacterium*

Substances

  • Fluoroquinolones
  • Amino Acids
  • DNA Gyrase