Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors

Porphyromonas gingivalis is one of the main etiological organisms in periodontal disease. On oral surfaces P.gingivalis is a component of multispecies biofilm communities and can modify the pathogenic potential of the community as a whole. Accumulation of P.gingivalis in communities is facilitated by interspecies binding and communication with the antecedent colonizer Streptococcus gordonii. In this study we screened a library of small molecules to identify structures that could serve as lead compounds for the development of inhibitors of P.gingivalis community development. Three small molecules were identified that effectively inhibited accumulation of P.gingivalis on a substratum of S.gordonii. The structures of the small molecules are derived from the marine alkaloids oroidin and bromoageliferin and contain a 2-aminoimidazole or 2-aminobenzimidazole moiety. The most active compounds reduced expression of mfa1 and fimA in P.gingivalis, genes encoding the minor and major fimbrial subunits, respectively. These fimbrial adhesins are necessary for P.gingivalis co-adhesion with S.gordonii. These results demonstrate the potential for a small molecular inhibitor-based approach to the prevention of diseases associated with P.gingivalis.