Therapeutic Establishment for Gingival Hyperplasia and Scar Formation by Use of Collagen-Digestible Proteases

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Porphyromonas gingivalis and Porphyromonas endodontalis, asaccharolytic black-pigmented anaerobes, are predominant pathogens of human chronic and periapical periodontitis, respectively. They incorporate di-and tri-peptides from the environment as carbon and energy sources. In the present study, we cloned a novel dipeptidyl peptidase(DPP) gene of P. endodontalis ATCC 35406, designated as DPP11. A homology search revealed the presence of a P. gingivalis orthologue, PGN0607, which has been categorized as an isoform of authentic DPP7. DPP11 specifically removed dipeptides from oligopeptides with the penultimate N-terminal Asp and Glu. Arg_<670> is a unique amino acid completely conserved in all DPP11 members, whilst this residue is converted to Gly in all authentic DPP7 members. Substitution analysis suggested that Arg_<670> interacts with an acidic residue of the substrate. Considered to preferentially utilize acidic amino acids, DPP11 ensures efficient degradation of oligopeptide substrates in these gram-negative anaerobic rods.In order to investigate the mechanism of Staphylococcal scalded skin syndrome(SSSS) caused by exfoliative toxin A(ETA), we expressed and purified ETA and its N-terminally truncated(Δ38 andΔ57) and inactive(Ser233Ala) derivatives in E. coli. Recombinant ETA(wt) showed the peptidase activity for LLE-MCA. This is the first report that ETA showed the peptidase activity other than Dsg1. ETA and its dirivatives exerted toxin activity to newborn mice, if ETA derivatives(wt andΔ38) possessed the peptidase activity, while ETAs with no peptidase activity(Δ57 and SerΔ233Ala) did not cause the disease. This finding indicated that the peptidase activity of ETA was indispensible for the toxin activity.