P. gingivalis, a gram negative anaerobe identified as one of the putative oral bacteria associated with severe, chronic forms of periodontal disease, is a successful colonizer of oral tissues, and can invade and remain viable for extended periods in primary gingival epithelial cells (GECs). P. gingivalis is capable of intracellular replication and modulates many phenotypic and signaling properties of GECs. Unlike many intracellular pathogens that are harmful to their host, P. gingivalis does not induce apoptotic or necrotic death in GECs. Furthermore, P. gingivalis infection protects GECs against apoptosis induced by potent pro-apoptotic agents. However, the mechanisms of inhibition of GECs cell death-signaling pathway(s) and the key upstream mediators along with biochemical and morphological alterations induced by P. gingivalis have not been characterized. In addition, the consequences of prolonged invasion of GECs by the microorganism with respect to its increasing ability to multiply and disseminate the infection within epithelium, as well as the fate of infected cells remain to be determined. Overall goal of this project is to delineate the long-term outcomes of P. gingivalis infection on host cell status. Specifically, ultimate fate of infected cells will be investigated by examining cell death-survival markers and phenotypic events throughout the infection. Underlying mechanism(s) of the modulation of apoptotic cell responses mediated by P. gingivalis will be characterized and the microorganism's ability to multiply and spread within epithelium over time and its relation to host cell survival will be determined. Flow cytometry, fluorescence microscopy, phospho-specific Western blotting-activation assays, RNA interference, and microarray based approaches will be employed to achieve these goals. Periodontal diseases are among the most prevalent polymicrobial diseases affecting a majority of US population and impose a significant burden on the health care system. Moreover, oral infections associated with P. gingivalis have been linked as potential risk factors to major systemic health problems such as cardiovascular disease, diabetes mellitus, stroke and premature births. Investigations of proposed aims will contribute to the conceptual framework of the P. gingivalis interaction with host cells and define more targeted approaches to control P. gingivalis associated diseases.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
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Lunsford, Dwayne
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University of Florida
Schools of Dentistry
United States
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Lee, Jaden S; Yilmaz, Özlem (2018) Unfolding Role of a Danger Molecule Adenosine Signaling in Modulation of Microbial Infection and Host Cell Response. Int J Mol Sci 19:
Lee, Kyulim; Roberts, JoAnn S; Choi, Chul Hee et al. (2018) Porphyromonas gingivalis traffics into endoplasmic reticulum-rich-autophagosomes for successful survival in human gingival epithelial cells. Virulence 9:845-859
Hung, Shu-Chen; Huang, Pei-Rong; Almeida-da-Silva, Cássio Luiz Coutinho et al. (2018) NLRX1 modulates differentially NLRP3 inflammasome activation and NF-?B signaling during Fusobacterium nucleatum infection. Microbes Infect 20:615-625
Lee, Jungnam; Roberts, JoAnn S; Atanasova, Kalina R et al. (2018) A novel kinase function of a nucleoside-diphosphate-kinase homologue in Porphyromonas gingivalis is critical in subversion of host cell apoptosis by targeting heat-shock protein 27. Cell Microbiol 20:e12825
Roberts, JoAnn S; Atanasova, Kalina R; Lee, Jungnam et al. (2017) Opportunistic Pathogen Porphyromonas gingivalis Modulates Danger Signal ATP-Mediated Antibacterial NOX2 Pathways in Primary Epithelial Cells. Front Cell Infect Microbiol 7:291
Lee, Jungnam; Roberts, JoAnn S; Atanasova, Kalina R et al. (2017) Human Primary Epithelial Cells Acquire an Epithelial-Mesenchymal-Transition Phenotype during Long-Term Infection by the Oral Opportunistic Pathogen, Porphyromonas gingivalis. Front Cell Infect Microbiol 7:493
Olsen, Ingar; Yilmaz, Özlem (2016) Modulation of inflammasome activity by Porphyromonas gingivalis in periodontitis and associated systemic diseases. J Oral Microbiol 8:30385
Bui, Fiona Q; Johnson, Larry; Roberts, JoAnn et al. (2016) Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1? and the danger signals ASC and HMGB1. Cell Microbiol 18:970-81
Morandini, Ana Carolina; Santos, Carlos F; Yilmaz, Özlem (2016) Role of epigenetics in modulation of immune response at the junction of host-pathogen interaction and danger molecule signaling. Pathog Dis 74:
Atanasova, Kalina; Lee, Jungnam; Roberts, JoAnn et al. (2016) Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome. Sci Rep 6:37643

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