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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2018, Vol. 38 Issue (11): 59-65    DOI: 10.13523/j.cb.20181108
综述     
CRISPR/Cas系统作为抗菌药的现状及展望 *
曾家伟,侯国锋,郑继平,杨诺,曾纪峰,郭桂英()
海南大学热带农林学院 海口 570228
The Progress of CRISPR/Cas System Used As Antimicrobials
Jia-wei ZENG,Guo-feng HOU,Ji-ping ZHENG,Nou YANG,Ji-feng ZENG,Gui-ying GUO()
Hainan University,Tropical Agriculture and Forestry College,Haikou 570228,China
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摘要：

抗生素长期滥用导致了人体内菌群失调及细菌耐药性的产生,因此需要寻找新型、靶向抗菌方法来治疗耐药细菌的感染。近年来,CRISPR/Cas系统的深入研究为设计特异性靶向耐药基因,定向清除耐药细菌的药物提供了新的思路。在此介绍了CRISPR/Cas系统作为新型抗菌方法,通过靶向切割抗性质粒或细菌基因组以实现对耐药基因或病原菌的特异性清除,并对CRISPR抗菌药的不同类型核酸酶的选择,以及CRISPR递送系统的运载工具进行了评价。
关键词： 细菌耐药性;  特异性清除;  CRISPR/Cas;  运载工具    
Abstract:

Antibiotics are used to arrest essential bacterial signaling and/or metabolic pathways,causing bacterial cell death.Overuse and misuse of antibiotics have led to dysbacteriosis and drug resistance.The application of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated) systems provides a new method to kill the drug-resistant microbes specifically by designing programmable sequence-specific antimicrobials.Currently,the most efficient CRISPR/Cas systems are type I and type II as a novel antimicrobial tool in selective removal of bacterial pathogens.Bacteriophage has been developed as a delivery vehicle,but the membrane vesicles had more potential for transporting the CRISPR/Cas systems into the targeted resistant pathogen.
Key words: Bacterial drug-resistance    Selective removal    CRISPR/Cas    Delivery vehicles
收稿日期: 2018-05-30 出版日期: 2018-12-06
ZTFLH:  Q522  
基金资助: * 国家自然科学基金(31460699);海南自然科学基金创新研究团队项目(2017CXTD005);海南自然科学基金面上项目 资助项目(317071)
通讯作者: 郭桂英     E-mail: 815827434@qq.com
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引用本文:

曾家伟,侯国锋,郑继平,杨诺,曾纪峰,郭桂英. CRISPR/Cas系统作为抗菌药的现状及展望 *[J]. 中国生物工程杂志, 2018, 38(11): 59-65.

Jia-wei ZENG,Guo-feng HOU,Ji-ping ZHENG,Nou YANG,Ji-feng ZENG,Gui-ying GUO. The Progress of CRISPR/Cas System Used As Antimicrobials. China Biotechnology, 2018, 38(11): 59-65.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20181108    或    https://manu60.magtech.com.cn/biotech/CN/Y2018/V38/I11/59

图1  酿脓链球菌的Cas9核酸酶(黄色)依靠sgRNA(红色)引导从而靶向目标DNA
图2  Cascade复合体结构(a) 和Cascade识别目标DNA序列示意图(b)[12]
图3  将CRISPR/Cas系统整合到噬菌粒或噬菌体基因组中,用于噬菌体的包装和细胞内传递[18]
图4  膜囊泡(MVs)介导的HGT
遗传物质
Genetic material		 供体细胞
Donor cells		 受体细胞
Recipient cells		 参考文献
Reference
革兰氏阴性菌
Gram-negative bacteria		 质粒DNA
Plasmid DNA		 淋病奈瑟氏菌
Neisseria gonorrhoeae		 淋病奈瑟氏菌
N. gonorrhoeae		 [36]
质粒与噬菌体DNA
Plasmid and phage DNA		 大肠杆菌
E. coli		 大肠杆菌
E. coli		 [37]
噬菌体DNA
Phage DNA		 大肠杆菌
E. coli		 沙门氏菌
Salmonella enterica		 [37]
质粒DNA
Plasmid and		 鲍曼不动杆菌
Acinetobacter baumannii		 鲍曼不动杆菌
A. baumannii		 [38]
质粒DNA
Plasmid and		 不动杆菌
Acinetobacter baylyi		 不动杆菌和大肠杆菌
A. baylyi and E. coli		 [29]
基因组
Chromosomal DNA		 牙龈卟啉单胞菌
Porphyromonas gingivalis		 牙龈卟啉单胞菌
P. gingivalis		 [39]
基因组与质粒DNA
Chromosomal DNA and plasmid DNA		 嗜热栖热菌和栖热菌
Scotoductus T. thermophiles and Thermus scotoductus		 嗜热栖热菌
T. thermophilus		 [40]
革兰氏阳性菌
Gram-positive bacteria		 基因组
Chromosomal DNA		 瘤胃球菌和白色瘤胃球菌
Ruminococcus sp. and Ruminococcus albus		 瘤胃球菌
Ruminococcus sp.		 [41]
表1  MVs介导的细菌之间水平基因转移[27]
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