Abstract
Bacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract. BV is characterized by replacement of health-associated Lactobacillus species by diverse anerobic bacteria, including the well-known Gardnerella vaginalis. Prevotella timonensis, and Prevotella bivia are anerobes that are found in a significant number of BV patients, but their contributions to the disease process remain to be determined. Defining characteristics of anerobic overgrowth in BV are adherence to the mucosal surface and the increased activity of mucin-degrading enzymes such as sialidases in vaginal secretions. We demonstrate that P. timonensis, but not P. bivia, strongly adheres to vaginal and endocervical cells to a similar level as G. vaginalis but did not elicit a comparable proinflammatory epithelial response. The P. timonensis genome uniquely encodes a large set of mucus-degrading enzymes, including four putative fucosidases and two putative sialidases, PtNanH1 and PtNanH2. Enzyme assays demonstrated that fucosidase and sialidase activities in P. timonensis cell-bound and secreted fractions were significantly higher than for other vaginal anerobes. In infection assays, P. timonensis efficiently removed fucose and α2,3- and α2,6-linked sialic acid moieties from the epithelial glycocalyx. Recombinantly expressed P. timonensis NanH1 and NanH2 cleaved α2,3 and α2,6-linked sialic acids from the epithelial surface, and sialic acid removal by P. timonensis could be blocked using inhibitors. This study demonstrates that P. timonensis has distinct virulence-related 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 anerobic bacteria in BV.
| Original language | English |
|---|---|
| Article number | e0069124 |
| Number of pages | 18 |
| Journal | mBio |
| Volume | 15 |
| Issue number | 9 |
| Early online date | 20 Aug 2024 |
| DOIs | |
| Publication status | Published - Sept 2024 |
Bibliographical note
Publisher Copyright:Copyright © 2024 Segui-Perez et al.
Funding
ZonMw (Netherlands Organisation for Health Research and Development) 91218017 Celia Segui-Perez
| Funders | Funder number |
|---|---|
| ZonMw (Netherlands Organisation for Health Research and Development) | 91218017 |
Keywords
- Hoylesella timonensis
- NanH
- Prevotella bivia
- Prevotella timonensis
- anerobic bacteria
- fucosidase
- mucus
- neuraminidase
- vaginal microbiota
- α2,3-linked sialic acids
- α2,6-linked sialic acids