Stafford, P., Higham, J., Pinnock, A. et al. (4 more authors) (2013) Gingipain-dependent degradation of mammalian target of rapamycin pathway proteins by the periodontal pathogen Porphyromonas gingivalis during invasion. Molecular Oral Microbiology, 28 (5). pp. 366-378. ISSN 2041-1006
Abstract
Porphyromonas gingivalis and Tannerella forsythia are gram-negative pathogens strongly associated with periodontitis. Their abilities to interact, invade and persist within host cells are considered crucial to their pathogenicity, but the mechanisms by which they subvert host defences are not well understood. In this study, we set out to investigate whether P. gingivalis and T. forsythia directly target key signalling molecules that may modulate the host cell phenotype to favour invasion and persistence. Our data identify, for the first time, that P. gingivalis, but not T. forsythia, reduces levels of intracellular mammalian target of rapamycin (mTOR) in oral epithelial cells following invasion over a 4-h time course, via the action of gingipains. The ability of cytochalasin D to abrogate P. gingivalis-mediated mTOR degradation suggests that this effect is dependent upon cellular invasion. We also show that levels of several other proteins in the mTOR signalling pathway are modulated by gingipains, either directly or as a consequence of mTOR degradation including p-4E-BP1. Taken together, our data suggest that P. gingivalis manipulates the mTOR pathway, providing evidence for a potentially novel mechanism by which P. gingivalis mediates its effects on host cell responses to infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 Wiley. This is an author produced version of a paper subsequently published in Molecular Oral Microbiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | degradation; gingipains; mammalian target of rapamycin; periodontitis; Porphyromonas gingivalis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Feb 2017 12:00 |
Last Modified: | 20 Mar 2018 23:31 |
Published Version: | https://doi.org/10.1111/omi.12030 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/omi.12030 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110833 |