Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease.

Abstract

Periodontal disease is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption and tooth loss. As periodontal disease progresses, oral treponemes (spirochetes) become dominant bacteria in periodontal pockets. Oral treponemes are anaerobes and all encode the enzyme pyruvate-ferredoxin oxidoreductase (PFOR) which catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA. Here we assess the susceptibility of oral treponemes to amixicile (AMIX), a novel inhibitor of PFOR. The minimum inhibitory concentration (MIC) of AMIX against several oral treponeme species was determined. The impact of AMIX on processes relevant to virulence including motility, H2 S production, and complement evasion were determined. The growth of all oral treponeme species tested was inhibited by AMIX with MIC concentrations (MIC) ranging from 0.5-1.5 μg/mL. AMIX significantly reduced motility, caused a dose-dependent decrease in hydrogen sulfide production and increased sensitivity to killing by human complement (i.e., serum sensitivity). AMIX is effective in vitro in inhibiting growth and other processes central to virulence. AMIX could serve could serve as a new selective therapeutic tool for the treatment of periodontal disease.