Desialylation of neisseria gonorrhoeae lipooligosaccharide by cervicovaginal microbiome sialidases: The potential for enhancing infectivity in men

Abstract

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.