The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.

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.

• Authors: 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
• Journal: EBioMedicine (EBioMedicine) Vol. 18 Pg. 236-243 (Apr 2017) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 28330602 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Glycoconjugates
• Immunoglobulin G
• Pneumococcal Vaccines
• Recombinant Fusion Proteins
• Glycerolphosphate Dehydrogenase

Topics

• Animals
• Bacterial Adhesion (physiology)
• Binding Sites
• Cell Line, Tumor
• Female
• Glycerolphosphate Dehydrogenase (genetics, immunology, metabolism)
• Glycoconjugates (chemistry, metabolism)
• Humans
• Immunoglobulin G (blood, immunology)
• Mice
• Molecular Dynamics Simulation
• Nasopharynx (microbiology)
• Pneumococcal Vaccines (immunology)
• Protein Structure, Tertiary
• Recombinant Fusion Proteins (biosynthesis, chemistry, immunology)
• Serogroup
• Streptococcus pneumoniae (enzymology, pathogenicity)
• Surface Plasmon Resonance