CRISPR-based genome editing for targeted reversal of bacterial antibiotic resistance: A literature review

Background: Antimicrobial resistance (AMR) is an escalating global health crisis that significantly undermines the effectiveness of existing antibiotics, threatening to render even common infections untreatable. As traditional drug development struggles to keep pace with emerging resistance, innovative therapeutic strategies are urgently needed. This literature review explores the potential of CRISPR-Cas systems, particularly CRISPR-Cas9, as precision genome-editing tools for combating bacterial antibiotic resistance. By specifically targeting and disrupting resistance-conferring genes—such as those encoding β-lactamases, efflux pump regulators, and antibiotic-modifying enzymes—CRISPR-Cas9 offers a promising approach to re-sensitize multidrug-resistant (MDR) bacteria to conventional antibiotics. The review highlights various delivery platforms, including bacteriophage vectors, conjugative plasmids, and nanoparticle-based carriers, that have been employed to introduce CRISPR constructs into pathogenic bacteria. Preclinical studies demonstrate successful gene disruption in key pathogens like Escherichia coli and Pseudomonas aeruginosa, resulting in restored antibiotic susceptibility. However, several challenges remain, including efficient and specific delivery, minimizing off-target effects, and addressing the potential for bacterial resistance to CRISPR itself. Emerging alternatives such as CRISPR-Cas12 and combinational CRISPR-phage systems show promise in overcoming these barriers. Overall, CRISPR-Cas technologies represent a transformative platform in antimicrobial therapy, with the potential to not only reverse resistance but also reshape the landscape of infectious disease treatment.