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一种可以选择肠道微生物的抗生素
Kristen A Muñoz1,2, Rebecca J Ulrich1,2, Archit K Vasan3,4,5
1Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Nature
|May 29, 2024
概括
一种新的抗生素, 洛拉米辛, 选择性地向格拉姆阴性病原体, 这一发现提供了一种有前途的策略,
科学领域:
- 微生物学
- 传染性疾病
- 药物发现
背景情况:
- 格拉姆阴性细菌感染是全球日益严重的健康问题.
- 目前的广泛抗生素会破坏肠道微生物群,增加二次感染的风险.
- 迫切需要选择性抗生素,
研究的目的:
- 设计和发现一种具有格兰负特异性的新型抗生素.
- 开发一种节约微生物的治疗药物.
- 建立未来抗生素开发的蓝图.
主要方法:
- 针对细菌脂蛋白运输系统的洛拉的设计.
- 对超过130种多药耐药的格拉姆阴性临床分离物进行测试.
- 在肺炎和败血症小鼠模型中评估洛胺的疗效.
- 对肠道微生物群和C. difficile殖民的影响的评估.
主要成果:
- 洛拉米辛对广泛的抗药性格拉姆阴性细菌表现出活性.
- 这种抗生素在临床前的小鼠感染模型中被证明有效.
- 洛拉米辛保护了小鼠的肠道微生物群,防止了二次Clostridioides difficile感染.
- 药物的选择性归因于病原体和初生动物之间的目标序列同质性差异.
结论:
- 洛拉是一种具有广谱活性的新型格拉姆阴性特异性抗生素.
- 这种抗生素有效治疗感染,
- 洛拉的选择性向策略为开发节约微生物群的抗生素提供了新的范例.
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