Previous studies have demonstrated that Neisseria gonorrhoeae sialylates the terminal N-acetyllactosamine present on its lipooligosaccharide (LOS) by acquiring CMP-N-acetyl-5-neuraminic acid upon entering human cells during infection. This renders the organism resistant to killing by complement in normal human serum. N-acetyllactosamine residues on LOS must be free of N-acetyl-5-neuraminc acid (Neu5Ac; also known as "sialic acid") in order for organisms to bind to and enter urethral epithelial cells during infection in men. This raises the question of how the gonococcus infects men if N-acetyllactosamine residues are substituted by Neu5Ac during infection in women. Here, we demonstrate that women with gonococcal infections have levels of sialidases present in cervicovaginal secretions that can result in desialylation of (sialylated) gonococcal LOS. The principle sialidases responsible for this desialylation appear to be bacterial in origin. These studies suggest that members of the cervicovaginal microbiome can modify N. gonorrhoeae, which will enhance successful transmission to men.

Neisseria gonorrhoeae causes the human-specific disease gonorrhea and is transmitted from person to person primarily via sexual contact. During transmission, N. gonorrhoeae is often exposed to seminal fluid and must adapt to this change in environment. Previous work demonstrated that seminal fluid facilitates N. gonorrhoeae motility and alters epithelial cell interactions. In this study, exposure to seminal fluid was found to decrease surface adherence of gonococci in a manner that was independent of Opa adhesin proteins or type IV pilus retraction. Semen was also shown to cause dispersal of bacteria that had previously established surface adherence. Although surface adherence decreased, interbacterial interactions were increased by seminal plasma both in long-term static culture and on a cell-to-cell basis over shorter time periods. The result of increased bacterium-bacterium interactions resulted in the formation of microcolonies, an important step in the N. gonorrhoeae infectious process. Seminal fluid also facilitated increased bacterial aggregation in the form of shear-resistant three-dimensional biofilms. These results emphasize the importance of the gonococcal response to the influx of seminal fluid within the genital niche. Further characterization of the N. gonorrhoeae response to semen will advance our understanding of the mechanisms behind the establishment of infection in naive hosts and the process of transmission. IMPORTANCE N. gonorrhoeae is the causative agent of the globally prevalent sexually transmitted infection gonorrhea. An understudied aspect of this human-adapted pathogen is the change in bacterial physiology that occurs during sexual transmission. N. gonorrhoeae encounters semen when transmitted from host to host, and it is known that, when N. gonorrhoeae is exposed to seminal fluid, alterations in bacterial motility and type IV pilus arrangement occur. This work extends our previous observations on this modulation of gonococcal physiology by seminal fluid and demonstrates that seminal plasma decreases surface adherence, promotes interbacterial interactions, and enhances biofilm formation.