Resident microbes shape the vaginal epithelial glycan landscape.
Kavita Agarwal, Biswa Choudhury, Lloyd S Robinson, Sydney R Morrill, Yasmine Bouchibiti, Daisy Chilin-Fuentes, Sara B Rosenthal, Kathleen M Fisch, Jeffrey F Peipert, Carlito B Lebrilla, Jenifer E Allsworth, Amanda L Lewis, Warren G Lewis
Author Information
Kavita Agarwal: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ORCID
Biswa Choudhury: Glycobiology Research and Training Center, UCSD, La Jolla, CA 92093, USA.
Lloyd S Robinson: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sydney R Morrill: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ORCID
Yasmine Bouchibiti: Department of Chemistry, University of California Davis, Davis, CA 95616, USA.
Daisy Chilin-Fuentes: Center for Computational Biology and Bioinformatics, UCSD, La Jolla, CA 92093, USA.
Sara B Rosenthal: Center for Computational Biology and Bioinformatics, UCSD, La Jolla, CA 92093, USA. ORCID
Kathleen M Fisch: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego (UCSD), La Jolla, CA 92093, USA. ORCID
Jeffrey F Peipert: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. ORCID
Carlito B Lebrilla: Department of Chemistry, University of California Davis, Davis, CA 95616, USA. ORCID
Jenifer E Allsworth: Department of Biomedical and Health Informatics, University of Missouri, Kansas City School of Medicine, Kansas City, MO 64110, USA.
Amanda L Lewis: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ORCID
Warren G Lewis: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ORCID
Epithelial cells are covered in carbohydrates (glycans). This glycan coat or "glycocalyx" interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis (BV) is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including , produce glycosyl hydrolase enzymes. However, glycans of the human vaginal epithelial surface have not been studied in detail. Here, we elucidate key characteristics of the "normal" vaginal epithelial glycan landscape and analyze the impact of resident microbes on the surface glycocalyx. In human BV, glycocalyx staining was visibly diminished in electron micrographs compared to controls. Biochemical and mass spectrometric analysis showed that, compared to normal vaginal epithelial cells, BV cells were depleted of sialylated - and -glycans, with underlying galactose residues exposed on the surface. Treatment of primary epithelial cells from BV-negative women with recombinant sialidases generated BV-like glycan phenotypes. Exposure of cultured VK2 vaginal epithelial cells to recombinant sialidase led to desialylation of glycans and induction of pathways regulating cell death, differentiation, and inflammatory responses. These data provide evidence that vaginal epithelial cells exhibit an altered glycan landscape in BV and suggest that BV-associated glycosidic enzymes may lead to changes in epithelial gene transcription that promote cell turnover and regulate responses toward the resident microbiome.
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