title: Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype.
abstract: Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes based on the diversity of the fimA genes encoding each fimbria subunit. It was suggested that P. gingivalis strains with type II fimbriae were more virulent than type I strains. For the present study, we generated the mutants in which fimA was substituted with different genotypes to study virulence of type II fimbriae. Using plasmid vectors, fimA of ATCC33277 (type I strain) was substituted with type II fimA, and that of OMZ314 (type II strain) with type I fimA. The substitution of type I fimA with type II enhanced bacterial adhesion/invasion to epithelial cells, whereas substitution with type I fimA resulted in diminished efficiency. Following bacterial invasion, type II clones swiftly degraded cellular paxillin and focal adhesion kinase, and inhibited cellular migration, whereas type I clones and DeltafimA mutants did not. BIAcore analysis demonstrated that type II fimbriae possess greater adhesive abilities for their receptor alpha5beta1-integrin than those of type I. In a mouse abscess model, the type II clones significantly induced serum IL-1beta and IL-6, as well as other infectious symptoms. These results suggest that type II fimbriae are a critical determinant of P. gingivalis virulence.
authors.affiliation: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kato
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakano
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Inaba
authors.forename: Masae
authors.initials: M
authors.lastname: Kuboniwa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsuda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Omori
authors.forename: Takashi
authors.initials: T
authors.lastname: Ooshima
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.forename: Atsuo
authors.initials: A
authors.lastname: Amano
mesh_terms: D000038:Abscess / Q000097:blood / Q000382:microbiology; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D016866:Bacteroidaceae Infections / Q000097:blood / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics*; D010861:Fimbriae, Bacterial / Q000235:genetics*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D039081:Integrin alpha5beta1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D051419:Paxillin / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000235:genetics* / Q000472:pathogenicity / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics
chemical_list: D039081:Integrin alpha5beta1; D053583:Interleukin-1beta; D015850:Interleukin-6; D051419:Paxillin; C063055:fimbrillin; D036781:Fimbriae Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases