Pharm.D. (six years)
Biomedical and Pharmaceutical Sciences
periodontal disease; 3D visualization; P. gingivalis; Gingipain R; drug-design
Periodontal disease is a common infection that damages gingival tissue and creates jawbone destruction that can lead to the loosening or loss of teeth. Hundreds of diverse bacterial species reside in the harsh environment of the oral cavity. The creation of plaque and biofilms serve to allow the bacteria to avoid immune-mediated destruction. This project analyzed periodontal disease pathogens using molecular printing 3D visualization. Two bacterial species (T. denticola and P. gingivalis) were chosen from the public resource: Research Collaboratory for Structural Bioinformatics: Protein Data Bank. T. denticola was a bacteria found to have a binding protein (FhbB) that structurally is hypothesized to enhance pathogenesis of the bacteria through depletion of the subgingival crevice and dysregulation of complement. The oral bacterial infection process is further shown by P. gingivalis; a bacterium that stimulates the production of increased inflammatory mediators and secretes a cysteine proteinase structure (Gingipain R). Gingipain R cleaves the inflammatory mediators into more active forms that create further gingival tissue destruction. Breakdown of tissue produces nutrients for oral bacterial growth leading to the overall progression of periodontal disease. Potential drug development, through computer modeling together with with 3D printing, was studied using the Gingipain R as a template for drugs to prevent progression of periodontitis. Systematic computer testing of benzamidine analog inhibitors have provided examples for future drug development to occur for the bacterial P. gingivalis proteinase. The field of periodontics is currently a clinical practice that is reactive to periodontal disease. Advanced drug therapies need development in mechanistic research as well as in drug-design to pharmacologically prevent the progression of periodontal disease.