(2015) Association of the invasion ability of Porphyromonasgingivalis with the severity of periodontitis, Virulence, 6:3, 274-281, DOI: 10.1080/21505594.2014 Keywords: cytokine proteolytic activity, invasion ability, Porphyromonas gingivalis, periodontitis, severityPorphyromonas gingivalis is one of the well-characterized periodontal pathogens involved in periodontitis. The invasive and proteolytic activities of P. gingivalis clinical isolates have been shown to be associated with heterogenic virulence, as determined in a mouse abscess model. The aims of the present study were to identify a P. gingivalis strain with a low virulence among clinical isolates, based on its invasive ability and cytokine proteolytic activities, and to explore the preferential degradation of a certain cytokine by P. gingivalis. P. gingivalis ATCC 33277, W50, and 10 clinical isolates were used. After incubating bacteria with IL-4, IL-6, IL-10, IL-17A, TNFa, IFNg, and IL-1a, the amounts of remaining cytokines were determined by ELISA. Invasion ability was measured by a flow cytometric invasion assay. There was inter-strain variability both in the cytokine proteolytic activities and invasion ability. In addition, differential degradation of cytokines by P. gingivalis was observed: while IFNg and IL-17A were almost completely degraded, inflammatory cytokines TNFa and IL-1a were less susceptible to degradation. Interestingly, the invasion index, but not cytokine proteolytic activities, of P. gingivalis had strong positive correlations with clinical parameters of subjects who harbored the isolates. Therefore, the invasive ability of P. gingivalis is an important virulence factor, and the bacterial invasion step may be a good target for new therapeutics of periodontitis.