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Infection and Immunity, May 2007, p. 2090-2100, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01013-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role for Gingipains in Porphyromonas gingivalis Traffic to Phagolysosomes and Survival in Human Aortic Endothelial Cells

Kumiko Yamatake,¹ Maki Maeda,^1, Tomoko Kadowaki,¹ Ryosuke Takii,¹ Takayuki Tsukuba,¹ Takashi Ueno,² Eiki Kominami,² Sadaki Yokota,³ and Kenji Yamamoto^1*

Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan,¹ Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan,² Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan³

Received 28 June 2006/ Returned for modification 15 August 2006/ Accepted 23 January 2007

Gingipains are cysteine proteinases that are responsible for the virulence of Porphyromonas gingivalis. Recent studies have shown that P. gingivalis is trapped within autophagic compartments of infected cells, where it promotes survival. In this study we investigated the role of gingipains in the intracellular trafficking and survival of this bacterium in human aortic endothelial cells and any possible involvement of these enzymes in the autophagic pathway. Although autophagic events were enhanced by infection with either wild-type (WT) P. gingivalis strains (ATCC 33277, 381, and W83) or an ATCC 33277 mutant lacking gingipains (KDP136), we have found that more than 90% of intracellular WT and KDP136 colocalized with cathepsin B, a lysosome marker, and only a few of the internalized cells colocalized with LC3, an autophagosome marker, during the 0.5- to 4-h postinfection period. This was further substantiated by immunogold electron microscopic analyses, thus implying that P. gingivalis evades the autophagic pathway and instead directly traffics to the endocytic pathway to lysosomes. At the late stages after infection, WT strains in phagolysosomes retained their double-membrane structures. KDP136 in these compartments, however, lost its double-membrane structures, representing a characteristic feature of its vulnerability to rupture. Together with the ultrastructural observations, we found that the number of intracellular viable WT cells decreased more slowly than that of KDP136 cells, thus suggesting that gingipains contribute to bacterial survival, but not to trafficking, within the infected cells.

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* Corresponding author. Mailing address: Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6337. Fax: 81-92-642-6342. E-mail: kyama{at}dent.kyushu-u.ac.jp

Published ahead of print on 12 February 2007.

Editor: J. B. Bliska

Present address: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.

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Infection and Immunity, May 2007, p. 2090-2100, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01013-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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• Elkaim, R., Werner, S., Kocgozlu, L., Tenenbaum, H. (2008). P. gingivalis Regulates the Expression of Cathepsin B and Cystatin C. JDR 87: 932-936 [Abstract] [Full Text]