Chronic periodontitis is a prevalent bacterially associated inflammatory disease of the supporting tissues of the tooth that is also associated with a range of systemic diseases and disorders. Porphyromonas gingivalis is regarded as a keystone pathogen of this polymicrobial disease. The virulence of Porphyromonas gingivalis is reported to be strain related. The aim of this study was to determine the genetic variability P. gingivalis strains sourced from panglobal geographical locations and determine if variability in virulence related proteins has a phylogenetic basis. Whole genome sequencing was performed on eleven strains and comparison made to ten previously sequenced strains. A single nucleotide polymorphism-based phylogenetic analysis distributed the strains into 3 clades. The main virulence factors of this bacterium are the gingipains, cell-surface associated cysteine proteinases with Arg-X (RgpA, RgpB) or Lys-X (Kgp) specificity. Both RgpA and Kgp have repetitive haemagglutinin-adhesin (HA) domains in the polypeptide region C-terminal to the catalytic domains that are known as cleaved adhesin domains (CADs). Only two highly conserved forms of the Kgp catalytic domain (Kgpcat) were found, and these were not associated with phylogenetic clustering of the strains. The two Kgpcat alleles differed by 21 specific amino acid substitutions in a 150 amino acid region that encompasses the catalytic site. These alleles divided the strains into two groups, those with relatively high Kgp activity and those with lower activity. The first three CADs C-terminal to Kgpcat displayed the same isoforms in the same order in all sequenced strains whilst there were three different isoforms of the fourth C-terminal CAD. The isoform of the C-terminal CAD present was unrelated to the isoform of Kgpcat.
In conclusion P. gingivalis uses specific domain rearrangements to generate diversity in specific surface proteins that is unrelated to phylogeny.