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使用工程结合CRISPR/Cas9系统重新敏感化对tigecycline和colistin耐药的大肠杆菌

Haijie Zhang^1,2, Bo Chen², Zeyu Wang²

¹Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, China.

Microbiology spectrum

|February 22, 2024

概括

一个新的CRISPR-Cas9系统使细菌对最后的抗生素tigecycline和colistin重新敏感. 这个系统有效地准和消除耐药基因,在体内将耐药细菌减少了99%以上.

科学领域:

分子生物学和遗传工程分子生物学和遗传工程
抗微生物耐药性研究的研究.
合成生物学中的应用.

背景情况:

提格环素和胆固醇是对抗卡巴耐药格拉姆阴性细菌感染的关键最后手段抗生素.
等离子体介导的tet (X4) 和mcr-1基因的出现,分别威胁着tigecycline和colistin的疗效.
迫切需要制定策略来对抗多药耐药 (MDR) 格拉姆阴性细菌并恢复抗生素的有效性.

研究的目的:

开发和评估一种基于CRISPR-Cas9的系统,用于重新敏感化对tigecycline和colistin耐药的细菌.
针对和消除特定的抗生素耐药性基因 (ARG),即tet (X4) 和mcr-1.
建立一种安全有效的治疗方法,在临床环境中对抗抗生素耐药性.

主要方法:

开发了一个结合式的CRISPR/Cas9系统,提供两个单导向RNA,准tet (X4) 和mcr-1基因.
为高效率 (近100%体外) 进行了优化结合,并在临床隔离物中实现了90%以上的复敏化.
使用基于谷氨酸的染色体,等离子体平衡的致命系统用于体内应用,以防止ARG传播.

主要成果:

克里斯普尔-卡斯9系统在使耐药细菌重新敏感方面表现出高的特异性和效率.
在体内给予该系统时,显著减少了对tigecycline和colistin耐药细菌的数量,达到1%.
该系统成功地使大肠杆菌中的tet-X4介导的tigecycline耐药性和mcr-1介导的colistin耐药性重新敏感化.

结论:

克里斯普尔-卡斯系统是有效的和可编程的抗微生物药物,用于使抗生素耐药菌株重新敏感.
这一策略提供了一种新的治疗方法,用于打击抗生素耐药性基因的传播.
开辟了开发基于CRISPR的选择性病原体消除和微生物组调节工具的新途径.

关键词:

克里斯普尔是什么意思?克里斯普尔是什么意思?抗生素耐药性抗生素耐药性 mcr-1-1 的使用情况.重新敏感化的重敏感化.(X) 的意思是

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