通过抑制一种基本的利博开关而活跃的基因负抗生素
Stephen E Motika, Rebecca J Ulrich, Emily J Geddes
1Department of Pathobiology, University of Illinois, Urbana, Illinois 61802, United States.
Journal of the American Chemical Society
|May 21, 2020
概括
研究人员将抗生素Ribocil C转化为有效向多抗药性格拉姆阴性感染. 这一突破使细菌能够大量积累, 为具有挑战性的感染提供了新的治疗策略.
科学领域:
- 微生物学
- 药物发现
- 抗菌药物耐药性
背景情况:
- 多种药物耐药的格拉姆阴性感染对全球健康构成重大威胁,治疗选择有限.
- 开发新的抗生素是很困难的,因为该化合物在阴性细菌中积累不良.
研究的目的:
- 改造抗生素Ribocil C以提高对格兰氏阴性病原体的积累和有效性.
- 评估弗拉单核酸 (FMN) 结合剂对格拉姆阴性细菌的转化潜力.
主要方法:
- 在大肠杆菌中使用化合物积累的预测指南.
- 修改了Ribocil C以提高其透和积聚在格拉姆阴性细菌中的能力.
- 评估了该化合物对格拉姆阴性临床分离物和小鼠感染模型的活性.
主要成果:
- 在大肠杆菌中成功转化为高度的Ribocil C化合物.
- 已证实改性Ribocil C对野生型Gram阴性病原体的全细胞活性.
- 在格拉姆阴性感染的小鼠模型中证实有效性.
结论:
- 研制的Ribocil C显示为一种新型治疗药物,
- 这项研究证实了使用预测指导方针开发针对格拉姆阴性细菌的抗生素的策略.
- 修改后的Ribocil C提供了进一步研究FMN核突开关结合剂在治疗格兰氏阴性感染的平台.
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