The diseases collectively known as periodontitis are bacterial infections. A small group of gram-negative oral bacteria are consistently associated with specific forms of disease. The presence of P. gingivalis is linked to chronic and severe adult periodontitis. P. gingivalis and the other periodontal pathogens are observed within diseased human gingiva, but the molecular mechanisms of attachment to, and penetration of, tissue are unknown. Previously, the applicant demonstrated, with quantitative data, that P. gingivalis attached to and invaded oral epithelial cells. A subsequent study showed that this organism was able to penetrate and divide within the cells of a multilayered pocket epithelium model. The current goal is to dissect the molecular events in the initial interactions between the bacterium and epithelial cells. This application focuses on the molecular mechanisms of attachment of P. gingivalis to epithelial cells. New data are presented on the in vitro modulation of attachment using P. gingivalis wild type and mutant strains. Data is also presented on P. gingivalis genes isolated after screening an expression library for clones which bound epithelial cells.
The specific aims of this application are to: 1) determine the P. gingivalis activities required for attachment to epithelial cells in vitro; 2) identify the bacterial genes involved in attachment; and 3) isolate P. gingivalis isogenic mutants defective in these genes. The cross-talk between P. gingivalis and the epithelial cell takes place at the attachment step, and the infection pathway is decided, in part, by the signaling between the two cell types. Therefore, attachment is the key target for preventative intervention strategies and understanding the molecular mechanisms of attachment is critical for the development of successful therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010510-03
Application #
2749324
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1996-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02142
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Boisvert, Heike; Duncan, Margaret J (2008) Clathrin-dependent entry of a gingipain adhesin peptide and Porphyromonas gingivalis into host cells. Cell Microbiol 10:2538-52
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Rodrigues, Paulo H; Progulske-Fox, Ann (2005) Gene expression profile analysis of Porphyromonas gingivalis during invasion of human coronary artery endothelial cells. Infect Immun 73:6169-73
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Nishikawa, Kiyoshi; Yoshimura, Fuminobu; Duncan, Margaret J (2004) A regulation cascade controls expression of Porphyromonas gingivalis fimbriae via the FimR response regulator. Mol Microbiol 54:546-60
Chen, Tsute; Duncan, Margaret J (2004) Gingipain adhesin domains mediate Porphyromonas gingivalis adherence to epithelial cells. Microb Pathog 36:205-9
Duncan, Margaret J (2003) Genomics of oral bacteria. Crit Rev Oral Biol Med 14:175-87
Chen, T; Nakayama, K; Belliveau, L et al. (2001) Porphyromonas gingivalis gingipains and adhesion to epithelial cells. Infect Immun 69:3048-56

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