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Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease
Author(s) -
Reed Lucas A.,
O'Bier Nathaniel S.,
Oliver Lee D.,
Hoffman Paul S.,
Marconi Richard T.
Publication year - 2018
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1002/jper.17-0185
Subject(s) - treponema denticola , microbiology and biotechnology , periodontitis , treponema , antimicrobial , chemistry , virulence , gingival and periodontal pocket , eikenella corrodens , bacteria , medicine , porphyromonas gingivalis , biology , biochemistry , immunology , genetics , syphilis , human immunodeficiency virus (hiv) , gene
Background 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. Methods 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, H 2 S production, and complement evasion were determined. Results 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). Conclusions 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.