重新利用防晒作为抗生素:激活的阿沃松抑制了耐美西林的金黄色葡萄球菌
Rachel M Andrews1, Gretchen E Bollar1, A Sophia Giattina1
1School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Metallomics : integrated biometal science
|August 31, 2023
概括
激活的阿沃 (AVB-Zn) 显示出强大的抗菌活性,对抗抗甲素耐药黄金葡萄球菌 (MRSA). 这种新的金属抗生素方法为对抗耐药细菌感染提供了一个有希望的新策略.
科学领域:
- 药用化学 医学化学
- 抗微生物耐药性 抗微生物耐药性
- 药物发现 药物发现 药物发现
背景情况:
- 耐甲基西林黄金葡萄球菌 (MRSA) 构成了严重的全球健康威胁,对最后手段抗生素的耐药性日益增加.
- 传统的高通量查方法在发现新的对MRSA有效的抗生素方面取得了有限的成功.
- 只有在金属离子化时活跃的金属抗生素,代表了一个替代的发现范式.
研究的目的:
- 研究阿沃松作为金属抗生素的潜在前体.
- 为了评估激活的avobenzone (AVB-Zn) 对MRSA的抗菌疗效.
- 在临床前模型中评估AVB-Zn的治疗潜力.
主要方法:
- 阿沃松被激活,形成AVB-Zn.
- 与临床MRSA分离物相比,确定了AVB-Zn的最小抑制度 (MIC).
- 细胞毒性测试是在人类细胞系上进行的.
- 在小鼠伤口感染模型中评估了疗效.
主要成果:
- 在没有的情况下,AVB-Zn表现出对MRSA分离物的强烈活性 (MIC:0.62-2.5μM),活性最小 (MIC:>10μM).
- AVB-Zn对抗抗菌素耐药的MRSA菌株是有效的.
- 在人类细胞中没有观察到显著的细胞毒性.
- 局部AVB-Zn乳液在MRSA伤口感染的小鼠模型中显示出有效性.
结论:
- 活性化 (AVB-Zn) 是一种强大的金属抗生素,有效对抗MRSA.
- 这种方法绕过了现有的阻力机制,并显示出了有利的安全概况.
- 在治疗MRSA感染方面,AVB-Zn是有前途的治疗候选药物.
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