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

EBioMedicine

David L. Gordon¹  Christopher J. Day²  Lauren E. Hartley-Tassell²  Michael P. Jennings²  Joe Tiralongo²  James C. Paton³  Melanie A. Higgins³  Abiodun D. Ogunniyi³  Layla K. Mahdi³  Adrienne W. Paton³ 

[1] Department of Microbiology and Infectious Diseases, Flinders University, Bedford Park, SA 5042, Australia;Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia;Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia;

关键词: Bacterial pathogens;    Streptococcus pneumoniae;    Protein vaccines;    Pneumococcal disease;    Colonization;    Adherence;    Host glycoconjugates;    Alpha-glycerophosphate oxidase;    Immunization;   

DOI  :  10.1016/j.ebiom.2017.03.002

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown