The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.
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.
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia.
Layla K
LK
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
MA
Higgins
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Christopher J
CJ
Day
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Joe
J
Tiralongo
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Lauren E
LE
Hartley-Tassell
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Michael P
MP
Jennings
Department of Microbiology and Infectious Diseases, Flinders University, Bedford Park, SA 5042, Australia.
David L
DL
Gordon
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia.
Adrienne W
AW
Paton
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia. Electronic address: james.paton@adelaide.edu.au.
James C
JC
Paton
Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia. Electronic address: david.ogunniyi@adelaide.edu.au.
Abiodun D
AD
Ogunniyi
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001665:Binding Sites; D045744:Cell Line, Tumor; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D056004:Molecular Dynamics Simulation; D009305:Nasopharynx / Q000382:microbiology*; D022242:Pneumococcal Vaccines / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000472:pathogenicity*; D020349:Surface Plasmon Resonance
D006001:Glycoconjugates; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; D005993:Glycerolphosphate Dehydrogenase
Adherence; Alpha-glycerophosphate oxidase; Bacterial pathogens; Colonization; Host glycoconjugates; Immunization; Pneumococcal disease; Protein vaccines; Streptococcus pneumoniae