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

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.

Investigating the genetic basis of disease resistance in animal populations

“…Other genes and pathways that were frequently studied in the review included those involved in the production of antimicrobial peptides, cytokines, and T-cell receptors. For example, numerous studies found that variations in genes responsible for the production of antimicrobial peptides were associated with disease resistance in various animal species, such as insects, fish, and cattle (21,22,23). Similarly, variations in genes involved in the production of cytokines and T-cell receptors were found to be associated with disease resistance in humans and other animal species.…”

The Antimicrobial Peptide LJ-hep2 from Lateolabrax japonicus Exerting Activities against Multiple Pathogenic Bacteria and Immune Protection In Vivo

“…This result is consistent with the previous findings that the peptides Sp-NPFin [ 35 ] from Scylla paramamosain and AS-hepc3 (48–56) [ 36 ] from A. schlegelii effectively inhibited the growth of several multi-drug resistant bacteria. Currently, AMPs are being explored as alternative therapy to tackle infections caused by multidrug-resistant bacteria [ 37 ]. Therefore, the antimicrobial activity of LJ-hep2 (66–86) against multidrug-resistant bacteria will provide more possibilities with regard to the exploration of potential anti-drug resistant bacterial drugs.…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…Class 1 comprises three types (I, III, and IV) and sixteen subtypes, whereas Class 2 includes three types (II, V, and VI) and seventeen subtypes [ 401 , 402 ]. The Class 1 CRISPR/Cas system takes on interference through the use of a multi-Cas effector protein complex, whereas Class 2 utilises a single effector protein responsible for the identification and cleavage of the target sequence [ 403 ]. Among the type II CRISPR/Cas systems, the most commonly studied effector protein is the DNA endonuclease Cas9 using a specificity-programming guide RNA (gRNA).…”