Abstract
Bacterial antimicrobial resistance (AMR) represents a global public health crisis that threatens to render conventional antibiotic regimens obsolete. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system has emerged as a revolutionary tool in molecular biology, offering unmatched sequence-specific genome-editing capabilities. By leveraging custom single-guide RNAs (sgRNAs), CRISPR/Cas9 can precisely target, cleave, or modify specific genomic and plasmid-borne resistance determinants, thereby neutralizing resistance pathways or directly inducing lethal double-strand breaks in pathogenic bacteria. Beyond simple gene disruption, CRISPR-based tools can eliminate resistance-carrying plasmids, block horizontal gene transfer (HGT), impair virulence pathways, and dismantle biofilm architectures while preserving commensal microflora. This narrative review provides a rigorous, updated synthesis of the structural and mechanical framework of CRISPR/Cas9, its targeted application across major multidrug-resistant (MDR) pathogens, a side-by-side analysis of various delivery systems, and the current balance of therapeutic promise against biological, ecological, and translational safety risks. Furthermore, we outline synergistic integrations with advanced nanocarriers, bacteriophage platforms, synthetic biology, and antimicrobial peptides (AMPs), laying out a prospective roadmap toward publishable clinical translation.