通过氨基糖化物对细菌持续存在的代谢物激活的消灭
Kyle R Allison1, Mark P Brynildsen, James J Collins
1Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for Biodynamics and Center for Advanced Biotechnology, Boston University, Boston, Massachusetts 02215, USA.
Nature
|May 13, 2011
概括
特定的代谢刺激可以杀死休眠的细菌,耐受抗生素. 这种方法增强了阿米诺糖化物对格拉姆阴性和格拉姆阳性细菌的疗效,有助于治疗慢性感染.
科学领域:
- 微生物学 微生物学
- 细菌生理学 细菌生理学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 细菌持久性是耐受抗生素的休眠细胞,有助于慢性和复发性感染.
- 目前的治疗方法缺乏有效的手段来消灭持久细胞.
- 持久性是治疗持久性细菌感染的一个重大挑战.
研究的目的:
- 研究消灭耐抗生素细菌的代谢策略.
- 为了确定代谢刺激是否可以增强氨基糖化物对持久性药物的疗效.
- 探索这种方法在治疗生物膜和慢性感染方面的潜力.
主要方法:
- 用氨基糖化物和特定的代谢刺激治疗格拉姆阴性 (大肠杆菌) 和格拉姆阳性 (金黄色葡萄球菌) 持续存在.
- 在有氧和无氧条件下杀死有效性的评估,独立于增长恢复.
- 研究涉及质子驱动力和氨基糖化物吸收的机制.
- 在小鼠尿路感染模型中测试组合疗法.
主要成果:
- 特定的代谢刺激增强了氨基糖化物对大肠杆菌和金黄色细菌的杀死.
- 强化是氨基糖体特异性的,不需要恢复生长,并在各种条件下起作用.
- 该机制涉及产生质子运动力,增强氨基糖化物吸收.
- 组合疗法有效地治疗了大肠杆菌和黄金色杆菌生物膜,并在小鼠感染模型中改善了结果.
结论:
- 代谢刺激提供了一种可行的策略,可以根除细菌的持续性,克服抗生素耐受性.
- 向细菌代谢可以提高现有的抗生素,如氨基甘油的有效性.
- 这种方法对治疗具有挑战性的持久性感染和生物膜具有前景.
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