Prevotella are major contributors of sialidases in the human vaginal microbiome

Author:

Pelayo Paula1ORCID,Hussain Fatima A.2,Werlang Caroline A.3,Wu Chloe M.3,Woolston Benjamin M.14,Xiang Claire M.1ORCID,Rutt Lindsay5,France Michael T.5,Ravel Jacques5ORCID,Ribbeck Katharina3,Kwon Douglas S.2ORCID,Balskus Emily P.16ORCID

Affiliation:

1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138

2. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Massachusetts General Hospital, Cambridge, MA 02139

3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139

4. Department of Chemical Engineering, Northeastern University, Boston, MA 02115

5. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201

6. HHMI, Harvard University, Cambridge, MA 02138

Abstract

Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and bacterial vaginosis (BV). 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 BV-associated organism Gardnerella vaginalis . Despite their implications for sexual and reproductive health, sialidases from other vaginal bacteria have not been characterized. Here, we show that vaginal Prevotella species produce sialidases that possess variable activity toward mucin substrates. The sequences of sialidase genes and their presence are largely conserved across clades of Prevotella from different geographies, hinting at their importance globally. Finally, we find that Prevotella sialidase genes and transcripts, including those encoding mucin-degrading sialidases from Prevotella timonensis , are highly prevalent and abundant in human vaginal genomes and transcriptomes. Together, our results identify Prevotella as a critical source of sialidases in the vaginal microbiome, improving our understanding of this detrimental bacterial activity.

Funder

Bill and Melinda Gates Foundation

NSF | National Science Foundation Graduate Research Fellowship Program

Publisher

Proceedings of the National Academy of Sciences

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