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使用抗菌肽和CRISPR/Cas9系统的多重耐药微生物疗法

Multidrug-Resistant Microbial Therapy Using Antimicrobial Peptides and the CRISPR/Cas9 System.

作者信息

Getahun Yared Abate, Ali Destaw Asfaw, Taye Bihonegn Wodajnew, Alemayehu Yismaw Alemie

机构信息

Livestock and Fishery Research Center, College of Agriculture, Arba Minch University, Arba Minch, Southern Nation Nationalities and Peoples Regional State, Ethiopia.

Department of Paraclinical Studies, College of Veterinary Medicine, Gondar University, Gondar City, Amhara Regional State, Ethiopia.

出版信息

Vet Med (Auckl). 2022 Aug 11;13:173-190. doi: 10.2147/VMRR.S366533. eCollection 2022.

Abstract

The emergence and spread of multidrug-resistant microbes become a serious threat to animal and human health globally because of their less responsiveness to conventional antimicrobial therapy. Multidrug-resistant microbial infection poses higher morbidity and mortality rate with significant economic losses. Currently, antimicrobial peptides and the CRISPR/Cas9 system are explored as alternative therapy to circumvent the challenges of multidrug-resistant organisms. Antimicrobial peptides are small molecular weight, cationic peptides extracted from all living organisms. It is a promising drug candidate for the treatment of multidrug-resistant microbes by direct microbial killing or indirectly modulating the innate immune system. The CRISPR/Cas9 system is another novel antimicrobial alternative used to manage multidrug-resistant microbial infection. It is a versatile gene-editing tool that uses engineered single guide RNA for targeted gene recognition and the Cas9 enzyme for the destruction of target nucleic acids. Both the CRISPR/Cas9 system and antimicrobial peptides were used to successfully treat nosocomial infections caused by ESKAPE pathogens, which developed resistance to various antimicrobials. Despite, their valuable roles in multidrug-resistant microbial treatments, both the antimicrobial peptides and the CRISPR/Cas systems have various limitations like toxicity, instability, and incurring high manufacturing costs. Thus, this review paper gives detailed explanations of the roles of the CRISPR/Cas9 system and antimicrobial peptides in circumventing the challenges of multidrug-resistant microbial infections, its limitation and prospects in clinical applications.

摘要

由于对传统抗菌治疗反应较弱,多重耐药微生物的出现和传播对全球动物和人类健康构成了严重威胁。多重耐药微生物感染导致更高的发病率和死亡率,并造成重大经济损失。目前,抗菌肽和CRISPR/Cas9系统被探索作为替代疗法,以应对多重耐药生物带来的挑战。抗菌肽是从小分子重量的阳离子肽,从所有生物体中提取。它是一种有前景的药物候选物,可通过直接杀灭微生物或间接调节先天免疫系统来治疗多重耐药微生物。CRISPR/Cas9系统是另一种用于管理多重耐药微生物感染的新型抗菌替代物。它是一种多功能基因编辑工具,使用工程化的单向导RNA进行靶向基因识别,并使用Cas9酶破坏靶核酸。CRISPR/Cas9系统和抗菌肽都被成功用于治疗由ESKAPE病原体引起的医院感染,这些病原体对各种抗菌药物产生了耐药性。尽管它们在多重耐药微生物治疗中发挥了重要作用,但抗菌肽和CRISPR/Cas系统都有各种局限性,如毒性、不稳定性和生产成本高。因此,本文详细解释了CRISPR/Cas9系统和抗菌肽在应对多重耐药微生物感染挑战中的作用、其局限性以及临床应用前景。

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