霍乱病毒CBASS菌体防御系统通过抗叶酸抗生素调节耐药性和杀死性
Susanne Brenzinger1, Martina Airoldi1,2, Adewale Joseph Ogunleye1
1Department of Microbiology, Biocenter, University of Würzburg, Würzburg, Germany.
Nature microbiology
|January 3, 2024
概括
霍乱病毒的有毒CBASS系统增强了抗叶酸抗生素的敏感性,将细菌静止药物转化为杀菌剂. 这种依赖叶酸结合的相互作用提供了新的抗微生物策略.
科学领域:
- 微生物学和分子生物学
- 发现抗微生物药物 发现抗微生物药物
- 细菌毒素系统 细菌毒素系统
背景情况:
- 毒素-抗毒素系统是具有抗菌潜力的有毒细菌模块,但临床应用有限.
- 基于循环寡核酸的抗菌素信号系统 (CBASS) 代表了另一类有毒细菌模块.
- 抗叶酸抗生素传统上具有细菌静止作用,抑制细菌生长而不是导致细胞死亡.
研究的目的:
- 研究Vibrio cholerae CBASS系统和抗叶酸抗生素之间的相互作用.
- 确定CBASS激活是否可以增强细菌静止抗生素的疗效.
- 阐明CBASS-抗叶酸相互作用背后的机制及其对抗微生物治疗的影响.
主要方法:
- 评估了CBASS激活对Vibrio cholerae中抗叶酸抗生素细菌敏感性的影响.
- 在用抗叶酸治疗后,DncV测量了循环寡核酸的产量,以确认CBASS激活.
- 通过检查相关的核样转移酶和叶酸结合口袋来研究相互作用的特异性.
- 分析了抗叶酸抗性基因对CBASS-抗叶酸相互作用的影响.
主要成果:
- 激活CBASS可使Vibrio cholerae对抗叶酸抗生素的敏感性增加多达10倍.
- 抗叶酸治疗导致DncV产生周期性寡核酸,表明CBASS激活.
- 这种相互作用是特定于具有类似叶酸结合口袋的CBASS系统,这表明抗叶酸释放DncV抑制.
- 抗叶酸抗性基因取消了相互作用,突出了与CBASS的潜在共同进化.
结论:
- 像CBASS这样的有毒细菌模块可以显著影响抗生素活性.
- CBASS赋予了古典的细菌静止抗叶酸抗生素杀菌活性.
- 这项研究揭示了增强抗生素疗效的新机制,并为新的抗菌战略提供了潜力.
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