Prevotellaare major contributors of sialidases in the human vaginal microbiome

Abstract

AbstractElevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and bacterial vaginosis. These negative effects may arise from sialidase-mediated degradation of the protective mucus layer in the cervicovaginal environment. Prior biochemical studies of vaginal bacterial sialidases have focused solely on the bacterial vaginosis-associated organismGardnerella vaginalis. Despite their implications for sexual and reproductive health, sialidases from other vaginal bacteria have not been characterized. Here, we show that vaginalPrevotellaspecies produce active sialidases that possess variable activity toward mucin. These sialidases are highly conserved across clades ofPrevotellafrom different geographies, hinting at their importance globally. Finally, we find thatPrevotellasialidases, including mucin-degrading enzymes fromPrevotella timonensis, are highly prevalent and abundant in human vaginal metagenomes and metatranscriptomes, Together, our results identifyPrevotellaas a critical source of sialidases in the vaginal microbiome, improving our understanding of this detrimental bacterial activity.Significance StatementSialidase activity in the vaginal microbiome is increased in bacterial vaginosis and strongly associated with other adverse health outcomes. Sialidase enzymes release sialic acid from host-derived glycans in the vaginal environment, altering their structures and functions. However, biochemical studies of vaginal bacterial sialidases have been limited to one genus,Gardnerella. In this work, we identify and characterize multiple active sialidase enzymes in vaginal bacteria of the genusPrevotella. We find thatPrevotellasialidases are more prevalent and abundant in vaginal microbial communities thanGardnerellasialidases. Our work highlightsPrevotellabacteria as an underappreciated source of sialidase activity with important implications for both our understanding of vaginal health and therapeutic development.