一种双功能的抗生素-载体结合物在消毒MRSA生物膜和杀死持久细胞方面表现出优异的活性
Alexandra Antonoplis1, Xiaoyu Zang1, Melanie A Huttner1
1Department of Chemistry , Stanford University , Stanford , California 94305 , United States.
Journal of the American Chemical Society
|November 3, 2018
概括
一种新的范素- 八素结合物 (V- r8) 有效地消灭了耐美西林金黄色葡萄球菌 (MRSA) 生物膜和持久细胞. 这种有前途的药物对抗生素不敏感的MRSA感染具有强烈的活性.
科学领域:
- 微生物学
- 传染性疾病
- 药物发现
背景情况:
- 耐甲基林黄金葡萄球菌 (MRSA) 构成严重的全球健康威胁,导致抗生素耐药性感染的高死亡率.
- 现有治疗方法对抗生素不敏感的细菌群体如生物膜和持续性细胞进行斗争.
研究的目的:
- 开发和评估一种针对MRSA,包括抗生素不敏感的形式的新型双重功能结合剂.
- 在实验室和体内检测范素-d-octaarginine结合物 (V-r8) 对MRSA的疗效.
主要方法:
- 范科米辛-d-octaarginine结合物的设计和合成 (V-r8).
- 在体外对MRSA生物膜和持续细胞进行V-r8的评估.
- 在小鼠伤口感染模型中对V-r8疗效的体内评估.
- 对V-r8的细胞积累和膜扰动性能的分析.
主要成果:
- 在实验室中,V- r8消除了MRSA生物膜和持续存在的细胞,显著超过了万科米辛.
- 在小鼠伤口感染模型中,V-r8消除了97%的生物膜相关的MRSA.
- 与万科米辛相比,结合剂显示细胞积累和膜干扰的增强.
- 没有观察到V-r8的急性皮肤毒性.
结论:
- 范素-d-octaarginine结合物 (V-r8) 是对抗生素不敏感的MRSA的一种强有力的药物.
- 由于其快速有效的活性,V-r8对治疗临床MRSA感染具有前景.
- 这种双重功能的结合物代表了对抗具有挑战性的MRSA感染的新策略.
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