TY - JOUR
T1 - The pneumococcal alpha-glycerophosphate oxidase enhances nasopharyngeal colonization through binding to host glycoconjugates
AU - Mahdi, Layla
AU - Higgins, Melanie
AU - Day, Christopher
AU - Tiralongo, Joe
AU - Hartley-Tassell, Lauren
AU - Jennings, Michael
AU - Gordon, David L
AU - Paton, Adrienne
AU - Paton, James
AU - Ogunniyi, David
N1 - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
KW - Adherence
KW - Alpha-glycerophosphate oxidase
KW - Bacterial pathogens
KW - Colonization
KW - Host glycoconjugates
KW - Immunization
KW - Pneumococcal disease
KW - Protein vaccines
KW - Streptococcus pneumoniae
UR - http://www.scopus.com/inward/record.url?scp=85015335389&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/565526
UR - http://purl.org/au-research/grants/NHMRC/1071659
UR - http://purl.org/au-research/grants/NHMRC/627142
U2 - 10.1016/j.ebiom.2017.03.002
DO - 10.1016/j.ebiom.2017.03.002
M3 - Article
VL - 18
SP - 236
EP - 243
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -