Chronic periodontal disease (PD) is an inflammatory condition that is highly widespread. Periodontal disease is a result of sub-gingival plaque pathogens, leading to alveolar bone loss. PD is also associated with diabetes, obesity, cardiovascular disease, respiratory disease, rheumatic arthritis and pre-term birth. The mechanism of periodontal infection is poorly understood due to the complexity of microbial factors, and highly complex inflammatory and anti-inflammatory signaling between pathogens and the host. New microbial pathogens are emerging that are resistant to conventional antibiotics; thus there is a need for drugs that are new class of antibiotics, and novel compounds that reduce pathogenicity of invading microbes. Pioneering studies in Frederick Ausubel's Laboratory (Harvard Medical School) have shown the effective use of C. elegans as a simple and powerful genetic model to screen for antimicrobial compounds, such as the discovery of RPW-24 that protects C. elegans from bacterial infections by modulating the p38 MAPK, and ATF7 transcription regulatory pathways [Pukkila-Worley et al. 2012]. We have previously used C. elegans to screen chemicals by using the nematode egg laying assay, and have identified novel compounds that affect egg laying behavior in a high throughput screen of commercially available chemical library [Siddiqui et al., C. elegans meeting UCLA, 2011]. We are screening chemical libraries in C. elegans for novel compounds that may inhibit the growth of oral pathogens such as Pseudomonas aeruginosa, found in the periodontal infections; and look for modulators of NSY-1, SEK-1, PMK-1 Mitogen Activated Protein (MAP) Kinase pathway that is comparable to the mammalian ASK-1(MAP kinase kinase kinase)/MKK3/6 (MAP kinase kinase) p38 MAP kinase signaling pathway. To validate the discovery of novel compounds in C. elegans high throughput screens for periodontal pathogens, we will use in vitro PLC (periodontal ligament cell) cell culture screens. Results will be presented on the efficacy of screened compounds on oral pathogens specific to chronic periodontal disease.

Affiliations:
- Northwestern University, Dept of BMBCB, Evanston, IL 60208
- UQU-DENT, UQ University, Makkah, SA