天然产品BO-1作为一个内部响应分子通过协同作用抑制抗微生物耐药的金黄色葡萄球菌

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Chuan-Yun Xiao¹, Jiao Huang¹, Xiao Liu¹

¹School of Pharmacy, Fudan University, Shanghai 201203, China.

ACS infectious diseases

|July 7, 2023

概括

来自Piper betle L.的一种新型化合物BO-1与抗生素协同作用,对抗多药耐药的金黄色葡萄球菌. 这种内部响应分子 (IRM) 抑制了排泄活动,恢复了对抗生素的敏感性,并减少了动物模型中的炎症.

科学领域:

微生物学微生物学
药理学药理学是指药理学的学科.
自然产品化学化学

背景情况:

耐多药金色葡萄球菌 (MRSA) 构成了全球健康的重大威胁,需要新的治疗策略.
现有的抗生素由于细菌耐药性机制,特别是排泄,效果越来越差.
内部响应分子 (IRM) 假设可以恢复抗生素敏感性,而不会诱导进一步的耐药性.

研究的目的:

来自Piper betle L.的IRM可以与抗生素对抗MRSA进行协同作用.
阐明已识别的IRM的作用机制,重点关注抵抗抑制.
在临床前模型中评估IRM-抗生素组合的治疗潜力.

主要方法:

从Piper betle L.中提取和分离化合物,使用色谱技术.
在实验室中测试孤立化合物的协同抗菌活性,以对抗耐药S. aureus菌株.
机理学研究涉及流量抑制试验和阻力逆转实验.
在S. aureus感染的动物模型中的体内疗效评估,评估细菌负载和炎症标志物.

主要成果:

从Piper betle L.提取物中分离出六种酸 (BO-1至BO-6) 的酸.
BO-1 显示出显著的协同活性,增强了西普罗洛克萨对多种耐药金黄色菌株的疗效.
机理学研究证实BO-1作为排泄抑制剂,抑制药物耐药性.
在受感染的小鼠中,用BO-1和西普罗夫洛克萨联合治疗逆转了抗生素耐药性和减少了炎症标记物 (IL-6,C反应蛋白).

结论:

博-1是一种强大的IRM,能够通过抑制排泄来恢复多药耐药的金黄色细菌对抗生素的敏感性.
结合BO-1和西普罗夫洛克萨,为克服抗生素耐药性和治疗黄金色杆菌感染提供了一个有希望的策略.
Piper betle L. 作为一种有价值的新型化合物来源,在打击抗菌素耐药性方面具有潜在应用.

关键词:

抗生素耐药性抗生素耐药性抗生素耐药的金黄色葡萄球菌酸酸 Ester 是一种酸.内部响应分子的内部响应分子这是一种协同作用的抗菌药物.

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