Sialidases derived from Gardnerella vaginalis remodel the sperm glycocalyx and impair sperm function

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiome, affects approximately 29 percent of women worldwide (up to 50% in some regions) and is associated with several adverse health outcomes including preterm birth and increased incidence of sexually transmitted infection (STI). BV-associated bacteria, such as Gardnerella vaginalis and Prevotella timonensis, damage the vaginal mucosa through the activity of sialidase enzymes that remodel the epithelial glycocalyx and degrade mucin glycoproteins. This damage creates an inflammatory environment which likely contributes to adverse health outcomes. However, whether BV-associated glycolytic enzymes also damage sperm during their transit through the reproductive tract has not yet been determined. Here, we show that sialidase-mediated glycocalyx remodeling of human sperm increases sperm susceptibility to damage within the female reproductive tract. In particular, we report that desialylated human sperm demonstrate increased susceptibility to complement lysis and agglutination, as well as decreased sperm transit through cervical mucus. Our results demonstrate a mechanism by which BV-associated sialidases may affect sperm survival and function and potentially contribute to adverse reproductive outcomes such as preterm birth and infertility.