通过向LDH来破坏细菌代谢,逆转Streptococcus suis的氨基糖化物耐药性
Shuji Gao1, Yingying Quan2, Shenao Song2
1College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471000, China; College of Life Science, Luoyang Normal University, Luoyang 471934, China; Henan Provincial Engineering Research Center for Detection and Prevention and Control of Emerging Infectious Diseases in Livestock and Poultry, Luoyang 471003, China.
International journal of antimicrobial agents
|August 22, 2025
概括
两种化合物,Panaxadiol (PD) 和维生素D2 (VD2),向Streptococcus suis乳酸脱酶,恢复对抗耐药细菌感染的氨基糖类的有效性.
科学领域:
- 微生物学
- 生物化学
- 药物发现
背景情况:
- 抗药性Streptococcus suis (S. suis) 的出现对全球健康构成威胁.
- 在农业和兽医中过度使用抗生素导致抗药性.
- 抗生素辅助剂提供一种增强现有药物的策略,
研究的目的:
- 识别和评估可以作为抗生素辅助剂的小分子.
- 研究已识别的化合物的代谢标和作用机制.
主要方法:
- 针对S. suis乳酸脱酶 (LDH) 的小分子选.
- 使用呼吸试验,NADH量化和质子动力 (PMF) 测量对Panaxadiol (PD) 和维生素D2 (VD2) 的代谢调节进行评估.
- 在体外和体内评估氨基糖化物吸收和杀菌活性.
主要成果:
- PD和VD2抑制了S. suis LDH,抑制了无氧代谢,并将pyruvate重定向到TCA循环中.
- 这种代谢转变增强了NADH的产生,放大了PMF,并增加了PMF依赖的氨基糖类的吸收.
- 这两种化合物与氨基甘油酸具有协同作用,在体外和动物模型中显著提高了对S. suis的杀菌效果.
结论:
- 用PD或VD2准S. suis的代谢途径可以恢复氨基糖化物敏感性.
- 这些化合物代表了对抗S. suis感染抗生素耐药性的有希望的辅助策略.
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