The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates
Layla K. Mahdi,
Melanie A. Higgins,
Christopher J. Day,
Joe Tiralongo,
Lauren E. Hartley-Tassell,
Michael P. Jennings,
David L. Gordon,
Adrienne W. Paton,
James C. Paton,
Abiodun D. Ogunniyi
Affiliations
Layla K. Mahdi
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia
Melanie A. Higgins
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia
Christopher J. Day
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia
Joe Tiralongo
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia
Lauren E. Hartley-Tassell
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia
Michael P. Jennings
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia
David L. Gordon
Department of Microbiology and Infectious Diseases, Flinders University, Bedford Park, SA 5042, Australia
Adrienne W. Paton
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia
James C. Paton
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia
Abiodun D. Ogunniyi
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia
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.
