Enzymatic Properties of Dipeptidyl Aminopeptidase IV Produced by the Periodontal PathogenPorphyromonas gingivalisand Its Participation in Virulence

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Abstract
Porphyromonas gingivalisis a major pathogen associated with adult periodontitis. We cloned and sequenced the gene (dpp) coding for dipeptidyl aminopeptidase IV (DPPIV) fromP. gingivalisW83, based on the amino acid sequences of peptide fragments derived from purified DPPIV. AnEscherichia colistrain overproducingP. gingivalisDPPIV was constructed. The enzymatic properties of recombinant DPPIV purified from the overproducer were similar to those of DPPIV isolated fromP. gingivalis. The three amino acid residues Ser, Asp, and His, which are thought to form a catalytic triad in the C-terminal catalytic domain of eukaryotic DPPIV, are conserved inP. gingivalisDPPIV. When each of the corresponding residues of the enzyme was substituted with Ala by site-directed mutagenesis, DPPIV activity significantly decreased, suggesting that these three residues ofP. gingivalisDPPIV are involved in the catalytic reaction. DPPIV-deficient mutants ofP. gingivaliswere constructed and subjected to animal experiments. Mice injected with the wild-type strain developed abscesses to a greater extent and died more frequently than those challenged with mutant strains. Mice injected with the mutants exhibited faster recovery from the infection, as assessed by weight gain and the rate of lesion healing. This decreased virulence of mutants compared with the parent strain suggests that DPPIV is a potential virulence factor ofP. gingivalisand may play important roles in the pathogenesis of adult periodontitis induced by the organism.