发现了可以选择性杀死代谢休眠细菌的抗生素
Erica J Zheng1, Jacqueline A Valeri2, Ian W Andrews3
1Program in Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Cell chemical biology
|November 29, 2023
概括
研究人员发现了semapimod,一种无毒的抗炎药物,对休眠细菌有效. 这种新的方法使用深度学习和静态阶段查来对抗慢性感染和抗生素耐药性.
科学领域:
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
- 计算生物学 计算生物学
背景情况:
- 慢性感染通常是由代谢休眠的细菌引起的,这些细菌对传统抗生素有抗性.
- 现有的抗生素发现方法优先考虑对活跃生长细胞有效的化合物,限制对休眠细菌的有效性.
- 对于针对休眠细菌的新型,无毒的抗生素来克服抗生素耐药性的急需.
研究的目的:
- 发现对代谢休眠细菌有效的无毒抗菌化合物.
- 开发和应用新的选方法,将静止相检测与深度学习结合起来.
- 识别具有治疗慢性感染的有利毒性概况的化合物.
主要方法:
- 利用静态相选方法识别对休眠细菌活性化合物.
- 采用深度学习驱动的虚拟屏幕用于化合物识别和毒性过.
- 综合微生物学分析,生物化学测量和单细胞显微镜以阐明作用机制.
主要成果:
- 鉴定了一种抗炎药物semapimod,作为对静止阶段*E. coli*和*A. baumannii*的强有力的化合物.
- 赛马皮莫德表现出良好的毒性概况,表明其作为安全治疗剂的潜力.
- 澄清的semapimod的作用机制:破坏和透的细菌外膜通过脂聚糖结合.
结论:
- 利用非传统的查方法和深度学习对于发现有效,无毒的抗菌化合物是有价值的.
- 赛马皮莫德代表了一种有前途的化合物,用于开发针对由休眠细菌驱动的慢性感染的新疗法.
- 这项研究强调了一种成功的策略,用于识别在感染相关的代谢不活跃细菌环境中有效的抗生素.
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