title: Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces protective immune response in mice.
abstract: For most bacteria, adherence to human cells is achieved by bacterial lectins binding to mammalian surface glyconjugates. 6-Phosphogluconate dehydrogenase (6PGD) was identified by us as one of Streptococcus pneumoniae cell wall lectin proteins, which elicits an age-dependent immune response in humans. This study assesses the role of 6PGD in S. pneumoniae pathogenesis as an adhesin and its ability to elicit a protective immune response in mice. Recombinant 6PGD (r6PGD) was cloned from S. pneumoniae serotype 3 (strain WU2). r6PGD interference in adhesion of three genetically unrelated unencapsulated pneumococcal strains (3.8, 14.8 and R6) and two genetically unrelated encapsulated pneumococcal strains (WU2 and D39) to A549 type II lung carcinoma cell was tested. BALB/c mice were immunized with r6PGD and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. r6PGD inhibited 90% and 80% of pneumococcal adhesion to the A549 cells of three unencapsulated S. pneumoniae strains and two encapsulated S. pneumoniae strains, respectively, in a concentration-dependent manner (P < 0.05). Antibodies to r6PGD produced in mice significantly inhibited bacterial adhesion to A549 cell (P < 0.05). Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge. We have identified 6PGD as a surface-located immunogenic lectin protein capable of acting as an adhesin. 6PGD importance to bacterial pathogenesis was demonstrated by the ability of r6PGD to elicit a protective immune response in mice.
authors.affiliation: Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, 84105 Israel.
authors.forename: D
authors.initials: D
authors.lastname: Daniely
authors.forename: M
authors.initials: M
authors.lastname: Portnoi
authors.forename: M
authors.initials: M
authors.lastname: Shagan
authors.forename: A
authors.initials: A
authors.lastname: Porgador
authors.forename: N
authors.initials: N
authors.lastname: Givon-Lavi
authors.forename: E
authors.initials: E
authors.lastname: Ling
authors.forename: R
authors.initials: R
authors.lastname: Dagan
authors.forename: Y
authors.initials: Y
authors.lastname: Mizrachi Nebenzahl
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001422:Bacterial Adhesion / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003001:Cloning, Molecular / Q000379:methods; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010734:Phosphogluconate Dehydrogenase / Q000276:immunology*; D040901:Proteomics; D011994:Recombinant Proteins / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000201:enzymology*; D014611:Vaccination / Q000379:methods; D014774:Virulence / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D010734:Phosphogluconate Dehydrogenase