It appears that only a few Gram-negative anaerobic bacteria, among the more than 700 microbial species known to exist in the human mouth, are associated with periodontal diseases. In addition, some of these organisms are also associated with cardiovascular and other systemic diseases. Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease. It produces several virulence factors (e.g., capsule, adhesin, membrane vesicles, and hydrolytic enzymes) that can contribute to its pathogenicity. The overall objective of our research program is to elucidate the molecular mechanism(s) for virulence regulation in P. gingivalis and examine the effects of these virulence factors on the host-microbe interaction. Our current research efforts are the following: (1) Studies on the mechanisms of virulence regulation in Porphyromonas gingivalis. (2) Oxidative stress resistance mechanisms in Porphyromonas gingivalis. (3) P. gingivalis - host interaction: gingipain-induced apoptosis.