Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase

Title of Dissertation: “Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase” Jonathan Andrew D’Ambrozio, Doctor of Philosophy, 2015 Thesis directed by: Ann E. Jerse, Ph.D. Professor, Department of Microbiology and Immunology 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 gyrA91/95 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 gyrA91/95 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