title: Single Amino Acid Polymorphisms of Pertussis Toxin Subunit S2 (PtxB) Affect Protein Function.
abstract: Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine. We investigated antigenic and functional differences of PtxB1 and PtxB2. The S2 protein was not very immunogenic. Only a few vaccinated or individuals infected with B. pertussis developed antibody responses to the S2 subunit, and these sera recognized both polymorphic forms equally well. Amino acid 18 of S2 is in a glycan binding domain, and the PtxB forms displayed differences in receptor recognition and toxicity. PtxB1 bound better to the glycoprotein, fetuin, and Jurkat T cells in vitro, but the two forms were equally effective at promoting CHO cell clustering. To investigate in vivo activity of Ptx, one μg of Ptx was administered to DDY mice and blood was collected on 4 days after injection. PtxB2 was more effective at promoting lymphocytosis in mice.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Millen
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Komatsu
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Yamaguchi
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nagasawa
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Haleigh
authors.initials: H
authors.lastname: Monaco
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D037342:Pertussis Toxin / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000633:toxicity; D011110:Polymorphism, Genetic; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D037342:Pertussis Toxin