Periodontal diseases are one of the most common bacterial infections of humans and impose a significant burden on the health care system. One of the predominant pathogens in periodontal disease is P. gingivalis;however, P. gingivalis can also inhabit the oral cavity in the absence of disease. The interaction between P. gingivalis and gingival epithelial cells makes a significant contribution to the degree of equilibrium between host and microbe, and to overall gingival health status. P. gingivalis can manipulate epithelial cell signal transduction pathways in order to direct entry into the host cell and to reprogram host innate immunity. One of the effector molecules of P. gingivalis is the HAD family serine phosphatase, SerB. The goal of this proposal is define the outcomes of the interaction between P. gingivalis and gingival epithelial cells as they relate colonization of the organism and the generation of immune dysbiosis. We shall also continue our major focus on the role of the functionally versatile SerB invasin and modulin of P. gingivalis. Cofilin, an actin depolymerizing protein, is required for P. gingivalis invasion. We will examine the ability of SerB to dephosphorylate and inactivate LIMK kinase which will lead to activation of cofilin. We will then investigate the impact of P. gingivalis on ROCK, PAK1 and MK2 pathways that lead to activation of LIMK. These interactions will be observed within the cell by live cell imaging. P..gingivalis can suppress IL-8 production in part through regulation of actin dynamics. We shall study the cofilin dependent, actin mediated suppression of IL-8 by P. gingivalis. The immune disruptive ability of P. gingivalis also extends to T-cell chemokines, and the mechanism of suppression of IP-10, ITAC and Mig will be studied. We will also begin to assess biological relevance by examining T-cell migration in response to epithelial cells infected with P. gingivalis. These studies will provide a detailed molecular analysis of the targeting of host signal transduction by P. gingivalis along with the role of a specific effector phosphatase. Ultimately, the knowledge gained could be developed into strategies that could be utilized to intervene in the P. gingivalis-epithelial cell interaction to ensure that the outcome is non-harmful to the host.

Public Health Relevance

P. gingivalis is a cause of periodontal diseases that afflict millions of Americans. In this study we will examine the interactions between P. gingivalis and the human cells that are colonized by the organism. The information to be gathered could be used to identify targets for novel therapeutic agents designed to interfere with the colonization and survival strategies of P. gingivalis.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lunsford, Dwayne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Louisville
United States
Zip Code
Lamont, Richard J; Hajishengallis, George (2015) Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 21:172-83
Inaba, Hiroaki; Sugita, Hideyuki; Kuboniwa, Masae et al. (2014) Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation. Cell Microbiol 16:131-45
Wang, Huizhi; Zhou, Huaxin; Duan, Xiaoxian et al. (2014) Porphyromonas gingivalis-induced reactive oxygen species activate JAK2 and regulate production of inflammatory cytokines through c-Jun. Infect Immun 82:4118-26
Hendrickson, Erik L; Wang, Tiansong; Beck, David A C et al. (2014) Proteomics of Fusobacterium nucleatum within a model developing oral microbial community. Microbiologyopen 3:729-51
Hajishengallis, George; Lamont, Richard J (2014) Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 44:328-38
Whitmore, Sarah E; Lamont, Richard J (2014) Oral bacteria and cancer. PLoS Pathog 10:e1003933
Moffatt-Jauregui, C E; Robinson, B; de Moya, A V et al. (2013) Establishment and characterization of a telomerase immortalized human gingival epithelial cell line. J Periodontal Res 48:713-21
Takeuchi, Hiroki; Hirano, Takanori; Whitmore, Sarah E et al. (2013) The serine phosphatase SerB of Porphyromonas gingivalis suppresses IL-8 production by dephosphorylation of NF-?B RelA/p65. PLoS Pathog 9:e1003326
Jauregui, Catherine E; Wang, Qian; Wright, Christopher J et al. (2013) Suppression of T-cell chemokines by Porphyromonas gingivalis. Infect Immun 81:2288-95
Dickinson, B C; Moffatt, C E; Hagerty, D et al. (2011) Interaction of oral bacteria with gingival epithelial cell multilayers. Mol Oral Microbiol 26:210-20

Showing the most recent 10 out of 25 publications