| Translocation of Porphyromonas gingivalis gingipain adhesin peptide A44 to host mitochondria prevents apoptosis. | |
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MedLine Citation:
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PMID: 20547744 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with periodontal diseases that, in some form, affect up to 80% of the U.S. population. The organism is highly proteolytic, and noncatalytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions. Recently, we showed that gingipain adhesin peptide A44 hijacks the host's clathrin-dependent endocytosis system, allowing the peptide and whole bacteria to be internalized by epithelial cells. In the present study, we found by cell fractionation assays and confocal microscopy that peptide A44 translocated to host mitochondria. Cell viability assays and quantitative real-time PCR showed that the peptide interacted with the cell death machinery by triggering upregulation of antiapoptotic factors bcl-2 and bcl-XL and prevented staurosporine-induced apoptosis for up to 12 h. We confirmed these findings with Western blot analyses of caspase-9 activation in time course experiments with staurosporine. Finally, we verified a similar antiapoptotic effect for P. gingivalis, showing for the first time that the organism manipulated mitochondrial functions during the first hours of infection, thus resisting host cell clearance by apoptosis of infected cells. This mechanism may enable the bacteria to persist in the protected cellular environment until the next step in pathogenesis, progression or resolution of infection. |
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Authors:
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Heike Boisvert; Margaret J Duncan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-14 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-19 Completed Date: 2010-08-06 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3616-24 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics, The Forsyth Institute, Boston, MA 02115, USA. hboisvert@forsyth.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adhesins, Bacterial
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metabolism* Apoptosis* Blotting, Western Caspase 9 / metabolism Cell Fractionation Cell Line Cell Survival Cysteine Endopeptidases / metabolism* Epithelial Cells / microbiology* Humans Microscopy, Confocal Mitochondria / metabolism* Porphyromonas gingivalis / immunology*, pathogenicity* Protein Transport Proto-Oncogene Proteins c-bcl-2 / biosynthesis Up-Regulation bcl-X Protein / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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R01-DE015931/DE/NIDCR NIH HHS; T32-DE007327-08/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adhesins, Bacterial; 0/BCL2L1 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.37/argingipain, Porphyromonas gingivalis |
| Comments/Corrections | |
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