细胞下抗生素可视化显示了受感染的巨细胞中的动态药物储存库
Daniel J Greenwood1, Mariana Silva Dos Santos1, Song Huang2
1The Francis Crick Institute, London, UK.
概括
结核药物贝达基林会积聚在宿主细胞的脂质滴中,作为一种可转移的储存体. 这种毒品在巨中增强了对结核菌的有效性.
科学领域:
- 微生物学
- 细胞生物学
- 药理学
背景情况:
- 结核病 (TB) 仍然是全球主要的传染病,由结核菌引起.
- 目前的多药结核化疗需要长时间的治疗 (≥6个月).
- 感染宿主细胞内的亚细胞抗生素局部化尚不清楚,这阻碍了治疗的优化.
研究的目的:
- 想象抗结核药物贝达基林在感染了Mycobacterium结核病的人类巨细胞中的亚细胞分布.
- 确定贝达基林是否能够透到所有含有细菌的细胞内.
- 研究宿主细胞有机体在毒品贩运和有效性的作用.
主要方法:
- 使用相关的光,电子和离子显微镜技术.
- 在受感染的人类巨细胞中以微米分辨率进行成像.
- 对贝达基林与菌根和宿主细胞的分布进行了分析.
主要成果:
- 发现贝达基林主要积聚在宿主细胞的脂质滴中.
- 药物在细胞内菌株的分布在各个区间中异质.
- 脂质滴作为可转移的储存器,增强抗菌活性而不是隔离药物.
结论:
- 宿主细胞的脂质滴在将贝达基林输送到细胞内结核菌中起着至关重要的作用.
- 强大的脂质结合促进药物输送到细胞内点,提高了抗菌治疗的疗效.
- 在亚细胞水平上了解药物与宿主相互作用是优化结核化疗的关键.
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