title: Abrogation of nontypeable Haemophilus influenzae protein D function reduces phosphorylcholine decoration, adherence to airway epithelial cells, and fitness in a chinchilla model of otitis media.
abstract: The pneumococcal polysaccharide conjugate vaccine which includes a nonacylated protein D carrier from Haemophilus influenzae has been recently licensed for use in many countries. While this vaccine is protective against nontypeable Haemophilus influenzae (NTHI)-induced acute otitis media (OM), the mechanism underlying this protective efficacy is not yet fully understood. Protein D/glycerophosphodiester phosphodiesterase (PD/GlpQ) is an outer membrane lipoprotein expressed by NTHI that has been ascribed several functions, including host cell adherence and phosphorylcholine (PCho) acquisition. We found that a pd/glpQ NTHI mutant exhibited reduced adherence to airway epithelial cells, diminished phosphorylcholine (PCho) decoration of biofilms, and compromised fitness during experimental acute OM compared to the parent strain. We also found that exposure of NTHI to antibodies directed against the vaccine formulation recapitulated the PCho decoration and NTHI adherence phenotypes exhibited by PD/GlpQ-deficient NTHI, providing at least two likely mechanisms by which the pneumococcal polysaccharide-PD/GlpQ conjugate vaccine induces protection from NTHI-induced OM.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Johnson
authors.forename: Glen
authors.initials: G
authors.lastname: McGillivary
authors.forename: Philippe
authors.initials: P
authors.lastname: Denoël
authors.forename: Jan
authors.initials: J
authors.lastname: Poolman
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002682:Chinchilla; D004847:Epithelial Cells / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000472:pathogenicity*; D006801:Humans; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D010033:Otitis Media / Q000382:microbiology*; D010767:Phosphorylcholine / Q000378:metabolism; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D007072:Immunoglobulin D; D008074:Lipoproteins; D037521:Virulence Factors; D010767:Phosphorylcholine; C067989:glpQ protein, Haemophilus influenzae