Molecular mechanism for connective tissue destruction by dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis.
Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.
Kumagai
Yumi
Y
Department of Microbiology, Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Yagishita
Hisao
H
Yajima
Ayako
A
Okamoto
Tatsuya
T
Konishi
Kiyoshi
K
D000818:Animals; D016866:Bacteroidaceae Infections / Q000382:microbiology / Q000503:physiopathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005347:Fibroblasts / Q000382:microbiology*; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010518:Periodontitis / Q000382:microbiology / Q000503:physiopathology; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence
D005353:Fibronectins; D005780:Gelatin; D003094:Collagen; D018819:Dipeptidyl Peptidase 4