Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase
Uniformed Services University Of The Health Sciences Bethesda United States
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With no vaccine available, control of gonorrhea is seriously threatened by the evolution of heightened antibiotic resistance. The fluoroquinolone class of antibiotics served as a first-line treatment option for gonorrhea for only a limited period of time due to the proliferation of resistance mutations. Resistance to fluoroquinolones in Neisseria gonorrhoeae is achieved in a two-step process in which mutations in the quinolone resistance-determining regions of the genes encoding GyrA and ParC confer intermediate and full resistance, respectively. A clinically relevant gyrA sub 9195 mutation was previously demonstrated by our laboratory to confer increased in vivo fitness to N. gonorrhoeae strain FA19, leading us to hypothesize that the resistance-conferring gyrA sub 9195 mutations are sufficient to alter the in vivo fitness of other N. gonorrhoeae strains. We found that the presence of this allele in two additional strains of N. gonorrhoeae FA1090 and MS11 not only enhanced in vivo fitness, but did so at a level that was 10-fold higher than that reported in strain FA19. We further speculated that the enhanced in vivo fitness phenotype arose through the altered enzymatic behavior of mutant DNA gyrase, leading to a transcriptional profile better suited for bacterial survival or growth within the host.