<p>How CRISPR-Cas System Could Be Used to Combat Antimicrobial Resistance</p>

Abstract

Rapid emergence of antibiotic-resistant bacteria has made it harder for us to combat infectious diseases and to develop new antibiotics. The clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) system, as a bacterial adaptive immune system, is recognized as one of the new strategies for controlling antibioticresistant strains. The programmable Cas nuclease of this system used against bacterial genomic sequences could be lethal or could help reduce resistance of bacteria to antibiotics. Therefore, this study aims to review using the CRISPR-Cas system to promote sensitizing bacteria to antibiotics. We envision that CRISPR-Cas approaches may open novel ways for the development of smart antibiotics, which could eliminate multidrug-resistant (MDR) pathogens and differentiate between beneficial and pathogenic microorganisms. These systems can be exploited to quantitatively and selectively eliminate individual bacterial strains based on a sequence-specific manner, creating opportunities in the treatment of MDR infections, the study of microbial consortia, and the control of industrial fermentation.

Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health

“…Significant developments in genetic engineering techniques can effectively help target and alter pathogenic bacterial genomes to recognize and mitigate drug resistance mechanisms. 188 , 189 The clustered regularly interspaced short palindromic repeats – CRISPR-associated (CRISPR-Cas) system, a bacterial adaptive immune system, is a newly recognized approach for controlling antibiotic-resistant strains, utilizing genomic engineering tools geared for gene knock-out and knock-in of sequence-specific DNA antibiotic targets. 189–191 The system is aimed to neutralize “the invasion by foreign genetic material” such as, bacteriophages, plasmids and transposons where the CRISPR-Cas9 acts as a “RNA-guided-DNA cutter”.…”

<p>Quorum Quenching: A Potential Target for Antipseudomonal Therapy</p>

“…Due to the increased antibiotic resistance among the human bacterial pathogens and the current poor effects of antibiotics to treat bacterial infections, finding novel alternative antimicrobial approaches is urgently needed. [5][6][7]33 Correspondingly, one of these approaches is targeting the expression of the QSregulated pathogenic factors using the analogs of the QS molecules. In this regard, they have been developed as Figure 1 The LuxR/AHL-mediated quorum sensing the regulation of the target genes' expressions in P. aeruginosa.…”

“…Therefore, there is an urgent need to find some novel antimicrobial agents and recognize novel approaches to treat or prevent bacterial infections. [4][5][6][7] The quorum sensing (QS) plays a critical role in multi-drug resistance of P. aeruginosa, which can upregulate both biofilms-associated matrix and efflux pump genes to improve resistance of bacteria against antibacterial agents. 8 A new promising approach to treat P. aeruginosa infections is its QS blocking without killing any of the target bacteria.…”

Applications of phage-derived RNA-based technologies in synthetic biology

“…8 c). Most of the CRISPR-Cas systems applied to combat antimicrobial resistance are based on their function of specifically targeting and cleave DNA sequences encoding antibiotic resistance genes, thereby reducing the bacterial antibiotic resistance [ [237] , [238] , [239] ]. A recent study aimed to develop a CRISPR-Cas13a system targeting transcripts of antimicrobial resistance genes to inhibit bacterial growth [ 240 ].…”