CRISPR-Cas9技术在细菌耐药性防控研究进展

CRISPR-Cas9 technology in the prevention and control of antibiotic resistance

摘要:

近年来，多种新型耐药基因的出现和全球性流行，严重威胁了全球公众健康。CRISPR-Cas9系统（clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 system）是细菌的一种适应性免疫系统，可切割耐药基因、抵御外来核酸入侵，现已作为一种新型基因编辑工具应用于防控细菌耐药性研究。本团队已建立了一种单质粒介导靶向mcr-1基因的CRISPR-Cas9系统，能有效并特异性消除黏菌素耐药大肠杆菌中的mcr-1，恢复其对黏菌素的敏感性。同时也发现在临床中应用还需要优化其递送方式。本文对近几年该技术在细菌耐药性防控方面的研究进展进行了综述，包括CRISPR-Cas9系统的发现过程、作用机制、递送方式、在体外检测实验结果的进展以及当前存在的问题等方面，以期为防控细菌耐药性提供新思路。

关键词:CRISPR-Cas9系统;细菌耐药性;基因定向编辑;细菌基因组;质粒

Abstract:

Recently, the emergence and global prevalence of many new antibiotic genes have led to a worldwide public health crisis. CRISPR-Cas9 (an adaptive immune system of bacteria) that can be used to cleave specific targets of resistant bacteria and against exogenous nucleic acid, serves a revolutionary gene editing tool to control antimicrobial resistance. Our previous study has established a plasmid-mediated CRISPR-Cas9 system targeting the mcr-1 gene, to efficiently and specifically eliminate mcr-1 gene and resensitize colistin resistant E. coli. Moreover, it is also necessary to optimize delivery methods of the CRISPR-Cas9 system for clinical treatment. This review focuses on the process of CRISPR-Cas9 technology in the prevention and control of antibiotic resistance in recent years, including the discovery process, mechanism, delivery method, advances in the experimental results in vitro and the existing problems, to provide new insights to the prevention and control of antibiotic resistance.

Key words:CRISPR-Cas9 system;antibiotic resistance;gene targeted editing;bacterial genome;plasmid