Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype

Cell Microbiol. 2007 Mar;9(3):753-65. doi: 10.1111/j.1462-5822.2006.00825.x. Epub 2006 Nov 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscess / blood
  • Abscess / microbiology
  • Animals
  • Bacterial Adhesion / genetics
  • Bacteroidaceae Infections / blood
  • Bacteroidaceae Infections / metabolism
  • Bacteroidaceae Infections / microbiology
  • Cell Line
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Female
  • Fimbriae Proteins / genetics*
  • Fimbriae, Bacterial / genetics*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Genotype
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Integrin alpha5beta1 / metabolism
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Mutation
  • Paxillin / metabolism
  • Porphyromonas gingivalis / genetics*
  • Porphyromonas gingivalis / pathogenicity
  • Porphyromonas gingivalis / ultrastructure
  • Virulence / genetics

Substances

  • Integrin alpha5beta1
  • Interleukin-1beta
  • Interleukin-6
  • Paxillin
  • fimbrillin
  • Fimbriae Proteins
  • Focal Adhesion Protein-Tyrosine Kinases