提供CRISPR-Cas9的非复制性菌素颗粒以准主要的blaCTX-M变异
Naiyaphat Nittayasut1, Teerapong Yata2, Sunisa Chirakul3
1Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
PloS one
|May 16, 2024
概括
克里斯普尔-卡斯9系统有效地通过禁用抗菌素耐药性 (AMR) 基因,使细菌对抗生素重新敏感. 菌体传递的CRISPR-Cas9向blaCTX-M基因显著减少了耐药细菌,恢复了抗生素的有效性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 抗菌素耐药性 (AMR) 构成全球健康威胁,需要新的治疗策略.
- 克里斯普尔-Cas9系统提供了一种精确的方法来准和禁用细菌基因,包括那些赋予AMR的细菌基因.
研究的目的:
- 评估通过体颗粒传递的CRISPR-Cas9系统在通过向blaCTX-M基因重新敏感化大肠杆菌对第三代胞素的有效性.
- 为了比较针对促进体区域的间隔器与blaCTX-M变异的内部序列的有效性.
主要方法:
- 编程CRISPR-Cas9系统具有针对blaCTX-M第1组和第9组变异及其促进物的特定间隔器.
- 使用非复制性法基米德粒子 (ΦRC319) 交付CRISPR-Cas9系统.
- 在大肠杆菌模型中对再敏感化和等离子体清除的评估.
主要成果:
- 针对blaCTX-M基因的内部序列的间隔器,但不是促进器区域,有效地调解了重新敏感化和等离子体清除.
- 观察到抗性细胞显著减少 (3-4 log10).
- 通过FRC319颗粒传递CRISPR-Cas9证明了对大肠杆菌的剂量依赖的重新敏感化.
结论:
- 当CRISPR-Cas9系统被适当的间隔器编程并由虫传递时,它可以有效地消除blaCTX-M基因.
- 这种方法有望通过逆转细菌的抗微生物耐药性来恢复第三代素的疗效.
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