Genetic Adaptation Contributing to Increased Gonococcal Fitness during Vaginal Infection of CEACAM-humanized Mice

Neisseria gonorrhoeae (Gc), the obligate human pathogen responsible for gonorrhea, has drastic consequences on reproductive health, if left untreated. Although, vaginal infection in wild-type mice can simulate asymptomatic colonization, important host-specific factors essential for human infection are overlooked. I utilize mice expressing human CEACAM3, CEACAM5, and CEACAM6, to reveal factors promoting mucosal colonization. By serial passaging Gc in the lower genital tract of these mice, I demonstrate a higher proportion of mice colonized in subsequent infections, suggesting selection for bacteria better capable of colonization. No changes in susceptibility of bacteria to low pH, complement-mediated killing or antimicrobial peptides, mCRAMP and mBD-1, were observed. Finally, a genome-wide analysis identified mutations acquired by in vivo adapted isolates. One mutation has previously been investigated as a promising vaccine target, validating the infection model and screening process. Further examination of other identified changes may provide insight into the Gc lifestyle within the genital mucosa.M.Sc