Periodontal diseases are complex chronic inflammatory conditions of tissues supporting the teeth resulting from the interaction between host and oral microflora. Microorganisms play a role in the initial stages of the diseases serving as a trigger for activation of the host inflammatory response. This involves complex set of interactions between the host and the bacteria, however to date the bacterial and the host components mediating these interactions remain not well understood. An essential step in initiating the infection involves adherence to host cells by the pathogens or their products. Bacterial cell surface proteins are the first to come in contact with the host environment and are most likely mediators of this process. Although much is known about aerobic outer membrane and cell surface proteins this knowledge is sparse regarding anaerobic bacteria. Anaerobes such as Porphyromonas gingivalis, Tannerella forsythensis, and Prevotella intermedia are implicated in development of periodontal diseases. We propose to investigate the role of cell surface proteins of the oral anaerobic bacteria in the first step of establishment of the microorganisms in the host: colonization of the oral cavity. Specifically, first we will characterize the Prev. intermedia 17 fibronectin-binding protein, AdpA. Second, using combination of cell labeling and proteomic approaches we will identify other cell surface proteins capable of binding to host components: e.g. salivary proteins, basal membrane proteins, and host cells. These proteins also will be further characterized to determine their role in mediating the attachment of Prev. intermedia to host components. The long-term objective of this application is to identify Prev. intermedia adhesins, which will further knowledge of mediators of the pathogenesis of the bacterium and ultimately lead to identification of potential anti-periodontitis vaccine candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016124-03
Application #
7274170
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2005-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$268,429
Indirect Cost
Name
Virginia Commonwealth University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Wunsch, Christopher M; Lewis, Janina P (2015) Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells. J Vis Exp :e53408
Anaya-Bergman, C; Rosato, A; Lewis, J P (2015) Iron- and hemin-dependent gene expression of Porphyromonas gingivalis. Mol Oral Microbiol 30:39-61
Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia et al. (2014) Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization. Infect Immun 82:2637-48
Yanamandra, S S; Sarrafee, S S; Anaya-Bergman, C et al. (2012) Role of the Porphyromonas gingivalis extracytoplasmic function sigma factor, SigH. Mol Oral Microbiol 27:202-19
Lewis, Janina P; Yanamandra, Sai S; Anaya-Bergman, Cecilia (2012) HcpR of Porphyromonas gingivalis is required for growth under nitrosative stress and survival within host cells. Infect Immun 80:3319-31
Singh, Amrita; Wyant, Tiana; Anaya-Bergman, Cecilia et al. (2011) The capsule of Porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence. Infect Immun 79:4533-42
Anaya-Bergman, Cecilia; He, Jia; Jones, Kevin et al. (2010) Porphyromonas gingivalis ferrous iron transporter FeoB1 influences sensitivity to oxidative stress. Infect Immun 78:688-96
Lewis, Janina P (2010) Metal uptake in host-pathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms. Periodontol 2000 52:94-116
Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin et al. (2010) AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein. Infect Immun 78:2385-96
Lewis, Janina P; Iyer, Divya; Anaya-Bergman, Cecilia (2009) Adaptation of Porphyromonas gingivalis to microaerophilic conditions involves increased consumption of formate and reduced utilization of lactate. Microbiology 155:3758-74