Development and characterization of anti-P. gingivalis peptides

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Periodontitis is the 6th most common infection worldwide and an estimated 5 – 20% of the population suffer from generalized chronic periodontitis. Studies based on the National Health and Nutrition Examination Survey (2009-2010) data demonstrated that the incidence of periodontitis is significantly higher in African Americans (AAs, 58.6%) and Hispanic Americans (HAs, 59.7%) compared to Caucasian Americans (CAs, 42.6%). Periodontitis may also have systemic health consequences leading to conditions such as cardiovascular disease, diabetes, and preterm birth, all of which are also considered disproportionally affect AAs and HAs. Microbiome is recently considered to be an important contributor to these health disparity diseases and conditions. Porphyromonas gingivalis, a gram-negative bacterium, has been recognized to play a vital role in the development of dysbiotic microbial communities and is capable of disrupting host-microbial homeostasis and inducing inflammatory responses in periodontal tissues facilitated by poly-microbes acting in concert. We recently identified a potential functional motif (SAPP), located at the C-terminal portion of S. cristatus ArcA, which can bind to surface proteins of P. gingivalis and repress the expression of fimA, mfa1 and rgps in P. gingivalis. These exciting findings provide the foundation for the proposed studies. Our overall hypothesis is that the components of the antagonistic communication system between S. cristatus and P. gingivalis can be developed to identify compounds that repress virulence factor expression and pathogenicity of P. gingivalis. The objective of this proposal is to dissect SAPP and identify the cognate P. gingivalis receptors. Therefore we will first characterize and design small peptides derived from SAPP that repress expression of virulence- associated genes in P. gingivalis. The receptor(s) of P. gingivalis that senses SAPP will then be identified and characterized. Successful completion of the proposed studies will provide fundamental novel information regarding interspecies antagonism, and could have far-reaching consequences on periodontal health by leading to discovery of potential pharmaceutical agents to inhibit P. gingivalis colonization and pathogenesis.