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

Yared Abate Getahun,1 Destaw Asfaw Ali,2 Bihonegn Wodajnew Taye,3 Yismaw Alemie Alemayehu4 1Livestock and Fishery Research Center, College of Agriculture, Arba Minch University, Arba Minch, Southern Nation Nationalities and Peoples Regional State, Ethiopia; 2Department of Paraclinical Studies, College of Veterinary Medicine, Gondar University, Gondar City, Amhara Regional State, Ethiopia; 3Faculty of Veterinary Medicine, College of Agriculture, Assosa University, Assosa City, Benshangul Gumez Regional State, Ethiopia; 4Department of Animal Science, College of Agriculture, Wollega University, Nekemtie City, Oromia Regional State, EthiopiaCorrespondence: Yared Abate Getahun, Email abateyared06@gmail.comAbstract: 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.Keywords: antimicrobial peptides, clinical applications, CRISPR/cas system, multidrug-resistant organism