结构-活动关系-激发了和脂肪酸作为新型胆固醇增强剂的发现
Jinju Cai1, Jingru Shi1, Chen Chen1
1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 8, 2023
概括
和脂肪酸,如甲酸,可以增强胆固醇.
科学领域:
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
- 生物化学 生物化学
背景情况:
- 移动胆固醇抗性基因 (mcr) 损害胆固醇的有效性.
- 胆固醇是一种最后的抗生素,用于难以治疗的感染.
- 抗生素组合策略可以扩大现有药物的效用.
研究的目的:
- 为了研究和脂肪酸 (SFAs) 作为辅助剂,以增强胆固醇活性.
- 为了评估SFA与胆固醇结合对mcr阳性细菌的疗效.
- 阐明SFA增强胆固醇抗菌作用的机制.
主要方法:
- 对多基因的结构-活性关系分析.
- 测试SFAs (特别是甲酸盐) 与胆固醇对mcr阳性细菌和生物膜的组合.
- 研究SFAs对脂聚糖 (LPS) 生物合成,MCR酶活性,细菌膜完整性和排泄的影响.
- 在三种动物感染模型中进行了体内疗效研究.
主要成果:
- 酸盐,特别是甲酸盐 (SC),显著增强对抗mcr阳性细菌的胆固醇活性.
- 这种SFA-胆固醇组合有效地抑制和消除细菌生物膜.
- SFA 防止移动素耐药性的出现和传播.
- 机制包括减少LPS修饰,增强膜损伤和损坏的排泄.
- 与胆固醇结合的SC在动物模型中显示出出色的治疗效果.
结论:
- 酸盐,特别是甲酸,是有前途的抗生素辅助剂.
- 这种组合策略为治疗多药耐药细菌引起的感染提供了潜力.
- SFAs可以帮助克服胆固醇耐药性,并扩大胆固醇的临床效用.
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