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Infection and Immunity, May 2005, p. 2655-2664, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2655-2664.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Mechanism for Connective Tissue Destruction by Dipeptidyl Aminopeptidase IV Produced by the Periodontal Pathogen Porphyromonas gingivalis

Yumi Kumagai,1 Hisao Yagishita,2 Ayako Yajima,1 Tatsuya Okamoto,3 and Kiyoshi Konishi1*

Department of Microbiology,1 Department of Pathology, Nippon Dental University, Tokyo,2 Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan3

Received 27 July 2004/ Returned for modification 19 October 2004/ Accepted 30 December 2004

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.


* Corresponding author. Mailing address: Department of Microbiology, Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. Phone: (81) 3 3261 8761. Fax: (81) 3 3264 8399. E-mail: konikiyo{at}tky.ndu.ac.jp.

Editor: V. J. DiRita


Infection and Immunity, May 2005, p. 2655-2664, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2655-2664.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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