Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype.
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.
Kato
Takahiro
T
Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Kawai
Shinji
S
Nakano
Kazuhiko
K
Inaba
Hiroaki
H
Kuboniwa
Masae
M
Nakagawa
Ichiro
I
Tsuda
Kayoko
K
Omori
Hiroko
H
Ooshima
Takashi
T
Yoshimori
Tamotsu
T
Amano
Atsuo
A
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
D039081:Integrin alpha5beta1; D053583:Interleukin-1beta; D015850:Interleukin-6; D051419:Paxillin; C063055:fimbrillin; D036781:Fimbriae Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases