Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA.
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA.
J Periodontol. 2018 Dec;89(12):1467-1474. doi: 10.1002/JPER.17-0185. Epub 2018 Sep 5.
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, H 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.
牙周病是一种多微生物感染，其特征为牙龈炎症、牙槽骨吸收和牙齿丧失。随着牙周病的进展，口腔密螺旋体（螺旋体）成为牙周袋中的优势细菌。口腔密螺旋体是厌氧菌，均编码丙酮酸-ferredoxin 氧化还原酶（PFOR），该酶催化丙酮酸的氧化脱羧为乙酰辅酶 A。在这里，我们评估了新型 PFOR 抑制剂 AMIX 对口腔密螺旋体的敏感性。
确定 AMIX 对几种口腔密螺旋体物种的最小抑菌浓度（MIC）。确定 AMIX 对与毒力相关的过程（包括运动性、H₂S 产生和补体逃避）的影响。
所有测试的口腔密螺旋体物种的生长均被 AMIX 抑制，MIC 浓度（MIC）范围为 0.5-1.5μg/ml。AMIX 显著降低了运动性，导致 H₂S 产生呈剂量依赖性下降，并增加了对人补体杀伤的敏感性（即血清敏感性）。
AMIX 在体外有效抑制生长和其他与毒力相关的过程。AMIX 可作为治疗牙周病的新的选择性治疗工具。
