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Observational study

Infectious Disease · 3 h ago

Gonococcal gyrA variants amplify zoliflodacin resistance associated with gyrB D429N

A laboratory study using an isogenic Neisseria gonorrhoeae panel found that ciprofloxacin resistance-associated gyrA variants modified resistance and fitness effects of gyrB D429N. Combined mutations increased zoliflodacin and ciprofloxacin minimum inhibitory concentrations, supporting surveillance for interacting resistance determinants.

Researchers investigated whether common ciprofloxacin resistance-associated gyrA variants influence the effects of the zoliflodacin resistance mutation gyrB D429N in Neisseria gonorrhoeae. Using a constructed isogenic bacterial panel, they assessed minimum inhibitory concentrations (MICs) and bacterial fitness across genetic backgrounds. The study addresses potential interactions between resistance determinants affecting two topoisomerase inhibitors; no patient outcomes were reported.

In strains carrying gyrB D429N, zoliflodacin MICs were two- to fourfold higher when ciprofloxacin resistance-associated gyrA alleles were also present. Conversely, gyrB D429N increased ciprofloxacin MICs in these strains three- to sixfold. The fitness cost of gyrB D429N ranged from modest to severe: costs were greatest in gyrA 91F/95G and 91F/95N backgrounds and comparatively minimal in the gyrA 91F/95A background.

These findings indicate that the consequences of a resistance mutation depend on the accompanying genetic background, supporting genomic surveillance for potentially high-risk combinations. However, laboratory MIC shifts and fitness measurements do not establish clinical treatment failure or transmission potential. Only the abstract was available; absolute MICs, panel size and detailed experimental methods were not provided.

AI summary · Not yet editor-reviewed

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