Abstract

Antimicrobial drug resistance within ESKAPE pathogens is a formidable global challenge, necessitating innovative solutions. This review explores a multifaceted strategy incorporating nanotechnology, CRISPR/Cas9, and other cutting-edge approaches to effectively combat multidrug resistance in ESKAPE bacteria. Nanotechnology presents a promising avenue through targeted drug delivery systems like antibiotic nanoparticles and antibiotic–antibody conjugates (AACs). While these nanostructures aim to enhance therapeutic efficacy and mitigate resistance spread, challenges such as anti-PEG antibodies and optimal drug release must be considered. Inspired by successful anticancer nanomedicines, nanotechnology seeks to optimize drug penetration and retention within infected tissues. The revolutionary CRISPR/Cas9 gene-editing technology offers a precise and tailored approach by selectively targeting and modifying bacterial resistance genes. This holds the potential to reverse or eliminate drug resistance in ESKAPE pathogens, though challenges like off-target effects and efficient delivery mechanisms require attention for clinical translation. Additionally, alternative approaches such as fecal microbial transplantation, bacteriophage therapy, and probiotic bacterial replacement are actively explored in clinical trials. These strategies diversify the arsenal against antibiotic resistance by targeting unique vulnerabilities in ESKAPE pathogens. A comprehensive and multidisciplinary strategy is imperative to effectively address antimicrobial drug resistance in ESKAPE pathogens. Integration of nanotechnology, CRISPR/Cas9, and emerging approaches offers a synergistic solution, holding promise in overcoming the challenges posed by these resilient multidrug-resistant bacteria. This review provides insights into current research, challenges, and potential breakthroughs, emphasizing the urgency for collaborative efforts to safeguard global health.

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