Abstract
AbstractBacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract (FRT). BV is characterized by replacement of health-associatedLactobacillusspecies by diverse anaerobic bacteria, including the well-knownGardnerella vaginalis.Prevotella timonensisandPrevotella biviaare anaerobes that are found in a significant percentage of BV patients, but their pathogenic properties are yet to be determined. Defining characteristics of anaerobic overgrowth in BV are adherence to the mucosal surface and the increased activity of mucin-degrading enzymes such as sialidases in vaginal secretions. Here, we demonstrate thatP. timonensisbut notP. biviastrongly adhered to vaginal and endocervical cells to a similar level asG. vaginalisbut did not elicit a comparable pro-inflammatory response. TheP. timonensisgenome uniquely encodes a large set of mucus-degrading enzymes including 4 putative fucosidases and 2 putative sialidases, PtNanH1 and PtNanH2. Enzyme assays demonstrated that fucosidase and sialidase activity inP. timonensiscell-bound and secreted fractions was significantly higher than for other vaginal anaerobes. Infection assays revealed thatP. timonensisfucosidases and sialidases efficiently removed fucose and α2,3- and α2,6-linked sialic acid moieties from the epithelial glycocalyx. Recombinantly expressedP. timonensisNanH1 and NanH2 efficiently removed α2,3 and α2,6-linked sialic acids from the epithelial surface and sialic acid removal byP. timonensiscould be blocked using inhibitors. This study demonstrates thatP.timonensishas distinct virulence properties that include initial adhesion and a high capacity for mucin degradation at the vaginal epithelial mucosal surface. Our results underline the importance of understanding the role of different anaerobic bacteria in BV.Significance statement (Layman)Bacterial vaginosis (BV) is a common vaginal infection that affects a high percentage of women and is associated with reduced fertility and increased risk of secondary infections.Gardnerella vaginalisis the most well-known BV-associated bacterium, butPrevotellaspecies includingP. timonensisandP. biviamay also play an important role. We showed that, similar toG. vaginalis,P. timonensisadhered well to the vaginal epithelium, suggesting that both bacteria could be important in the first stage of infection. Compared to the other bacteria,P. timonensiswas unique in efficiently removing the protective mucin sugars that cover the vaginal epithelium. These results underscore that vaginal bacteria play different roles in the initiation and development of BV.
Publisher
Cold Spring Harbor Laboratory
Cited by
3 articles.
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