CRISPR-Cas9 system: A potent tool to fight antibiotic resistance in bacteria

One of the most challenging concerns for modern medical practitioners is to deal with infections caused by the ever-increasing number of antibiotic-resistant bacteria (ARB). New antibiotics are not coming up in that pace, as their development is a tedious and time-consuming process with limited economic benefits for pharma companies. Among the various strategies tested to combat ARB, CRISPR-Cas9-based therapy is the most novel and foolproof. The CRISPR-Cas9 system is a recently discovered indigenous defense mechanism, identified in most archaeal and bacterial members that immunize and protect the cell against a second invasion from bacteriophage or plasmid DNA attack. These prokaryotic members, using an endogenous Cas9 protein guided by a unique short RNA sequence (∼20 nts) processed from earlier foreign DNA encounters, targets and destroys the invasive DNA. The CRISPR-Cas9 system has the potential and flexibility to be used as a gene-editing tool to modify antibiotic resistant or exclusive house-keeping genes on plasmids or genomes of specific pathogens, thereby resensitizing them to the antibiotics or even killing them. As the system is highly specific in its action, it can even target specific pathogenic bacteria in the infection site without harming the entire microbial population. This review first highlights the potential threats of ARB, particularly those in the priority list, and then elucidates how RNA-guided CRISPR-Cas9-based therapy can be used to fight them, covering most of the technicalities involved in the process. • Antibiotic resistant ESKAPE pathogens are major concerns. • CRISPR-Cas9-based gene editing is precise, flexible and foolproof. • CRISPR-Cas9 system can target DNA/RNA with guide RNA and Cas9 protein. • Targeting endogenous genes ARB can be controlled by CRISPR-Cas9. • Optimizations are needed to establish CRISPR-Cas9 gene therapy in clinical studies.