The pneumococcal alpha-glycerophosphate oxidase enhances nasopharyngeal colonization through binding to host glycoconjugates

Layla Mahdi, Melanie Higgins, Christopher Day, Joe Tiralongo, Lauren Hartley-Tassell, Michael Jennings, David L Gordon, Adrienne Paton, James Paton, David Ogunniyi

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.

    Original languageEnglish
    Pages (from-to)236-243
    Number of pages8
    JournalEBioMedicine
    Volume18
    DOIs
    Publication statusPublished - Apr 2017

    Bibliographical note

    This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Keywords

    • Adherence
    • Alpha-glycerophosphate oxidase
    • Bacterial pathogens
    • Colonization
    • Host glycoconjugates
    • Immunization
    • Pneumococcal disease
    • Protein vaccines
    • Streptococcus pneumoniae

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