CRISPR–Cas-Mediated Reprogramming Strategies to Overcome Antimicrobial Resistance

TL;DR

CRISPR technology can target and eliminate antibiotic resistance genes in bacteria, offering a new way to treat infections and prevent the spread of resistance.

Contribution

The paper highlights CRISPR-based strategies as a novel approach to combat antimicrobial resistance by directly targeting resistance genes and mobile genetic elements.

Findings

CRISPR systems can restore antibiotic susceptibility by eliminating resistance genes.

CRISPR can suppress horizontal gene transfer by removing plasmids and other mobile genetic elements.

Advances in delivery platforms and Cas protein engineering are improving the translational potential of CRISPR-based antimicrobials.

Abstract

Antimicrobial resistance (AMR) is escalating worldwide, posing a serious threat to global public health by driving infections that are no longer treatable with conventional antibiotics. CRISPR–Cas technology offers a programmable and highly specific therapeutic alternative by directly targeting the genetic determinants responsible for resistance. Various CRISPR systems can restore antibiotic susceptibility and induce selective bactericidal effects by eliminating resistance genes, disrupting biofilm formation, and inhibiting virulence pathways. Moreover, CRISPR can suppress horizontal gene transfer (HGT) by removing mobile genetic elements such as plasmids, thereby limiting the ecological spread of AMR across humans, animals, and the environment. Advances in delivery platforms—including conjugative plasmids, phagemids, and nanoparticle-based carriers—are expanding the translational potential of CRISPR-based antimicrobial strategies. Concurrent progress in Cas protein engineering, spatiotemporal activity regulation, and AI-driven optimization is expected to overcome current technical barriers. Collectively, these developments position CRISPR-based antimicrobials as next-generation precision therapeutics capable of treating refractory bacterial infections while simultaneously suppressing the dissemination of antibiotic resistance.

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