title: Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors.
abstract: 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.
authors.affiliation: Oral Health and Systemic Disease, University of Louisville, Louisville, KY, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wright
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: R J
authors.initials: RJ
authors.lastname: Melander
authors.forename: C
authors.initials: C
authors.lastname: Melander
authors.forename: R J
authors.initials: RJ
authors.lastname: Lamont
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D013437:Carbon-Sulfur Lyases / Q000187:drug effects; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D007093:Imidazoles / Q000494:pharmacology; D056265:Microbial Interactions; D018613:Microscopy, Confocal / Q000379:methods; D018933:Pili, Sex / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D054852:Small Molecule Libraries; D054773:Streptococcus gordonii / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001562:Benzimidazoles; D007093:Imidazoles; C545438:Mfa1 protein, Porphyromonas gingivalis; D011758:Pyrroles; D054852:Small Molecule Libraries; C514118:ageliferin; C063055:fimbrillin; D036781:Fimbriae Proteins; C014973:2-aminoimidazole; C027391:2-aminobenzimidazole; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria; C077209:oroidin
keywords: biofilms; fimbriae; periodontal disease; porphyromonas; streptococcus