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J Infect Dis 2012 Jun;205(12):1821-9

Impact of fluoroquinolone resistance mutations on gonococcal fitness and in vivo selection for compensatory mutations.

Kunz AN, Begum AA, Wu H, D'Ambrozio JA, Robinson JM, Shafer WM, Bash MC, Jerse AE

Abstract

Background.¿Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA(91/95) and parC(86) mutations on gonococcal fitness. Methods.¿Mutant gyrA(91/95) and parC(86) alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR(-79) mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results.¿In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA(91/95) mutation conferred an in vivo fitness benefit to wild-type and mtrR(-79) mutant gonococci. The gyrA(91/95), parC(86) mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA(91/95), parC(86), mtrR(-79) mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (Cip(R)) mutant was selected during infection with the gyrA(91/95), parC(86), mtrR(-79) mutant in which the mtrR(-79) mutation was repaired and the gyrA(91) mutation was altered. This in vivo-selected mutant grew as well as the wild-type strain in vitro. Conclusions.¿gyrA(91/95) mutations may contribute to the spread of QRNG. Further acquisition of a parC(86) mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain Cip(R).


Category: Journal Article
PubMed ID: #22492860 DOI: 10.1093/infdis/jis277
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2012-06-20 Entry Last Modified: 2012-08-29
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