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Infection and Immunity, October 2009, p. 4187-4196, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments

Nobumichi Furuta,¹ Kayoko Tsuda,^1, Hiroko Omori,² Tamotsu Yoshimori,² Fuminobu Yoshimura,³ and Atsuo Amano^1*

Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan,¹ Department of Cellular Regulation, Division of Cellular and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita-Osaka, Japan,² Department of Microbiology, School of Dentistry, Aichi-Gakuin University, Nagoya-Aichi, Japan³

Received 5 January 2009/ Returned for modification 31 March 2009/ Accepted 27 July 2009

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including major fimbriae and proteases termed gingipains, although it is not confirmed whether MVs enter host cells. In this study, we analyzed the mechanisms involved in the interactions of P. gingivalis MVs with human epithelial cells. Our results showed that MVs swiftly adhered to HeLa and immortalized human gingival epithelial cells in a fimbria-dependent manner and then entered via a lipid raft-dependent endocytic pathway. The intracellular MVs were subsequently routed to early endosome antigen 1-associated compartments and then were sorted to lysosomal compartments within 90 min, suggesting that intracellular MVs were ultimately degraded by the cellular digestive machinery. However, P. gingivalis MVs remained there for over 24 h and significantly induced acidified compartment formation after being taken up by the cellular digestive machinery. In addition, MV entry was shown to be mediated by a novel pathway for transmission of bacterial products into host cells, a Rac1-regulated pinocytic pathway that is independent of caveolin, dynamin, and clathrin. Our findings indicate that P. gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis.

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* Corresponding author. Mailing address: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan. Phone: 81-6-6879-2976. Fax: 81-6-6879-2110. E-mail: amanoa{at}dent.osaka-u.ac.jp

Published ahead of print on 3 August 2009.

Editor: V. J. DiRita

Present address: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, Yahaba-Iwate 028-3694, Japan.

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Infection and Immunity, October 2009, p. 4187-4196, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Furuta, N., Takeuchi, H., Amano, A. (2009). Entry of Porphyromonas gingivalis Outer Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment. Infect. Immun. 77: 4761-4770 [Abstract] [Full Text]