MINI REVIEW article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicDefending the Last Line: Combatting Carbapenem-Resistant PathogensView all 10 articles
CRISPR–Cas Systems against Carbapenem Resistance: From Proof-of-Concept to Clinical Translation
Provisionally accepted
- 1General Hospital of Volos, Volos, Greece
- 2Diethnes Panepistemio tes Ellados, Thessaloniki, Greece
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Carbapenem-resistant Enterobacterales (CRE) pose a major global threat, driven by plasmid-borne carbapenemase genes such as blaKPC, blaNDM and blaOXA-48. CRISPR–Cas systems offer programmable strategies to selectively eliminate these resistance determinants. This mini-review summarizes recent advances in Cas9-based plasmid curing, RNA-targeting approaches such as Cas13a and Cas13d, and DNA-targeting Cas3-enhanced bacteriophage therapeutics that have entered early clinical evaluation. Particular attention is given to conjugative CRISPR–Cas9 plasmid systems, which enable targeted plasmid eradication without laboratory transformation and broaden the delivery toolbox beyond phage vectors. We further discuss major translational challenges, including delivery efficiency, phage host-range constraints, ecological risks of horizontal CRISPR dissemination, and off-target effects. Finally, we highlight emerging delivery platforms—outer membrane vesicles, lipid and polymeric nanoparticles, conjugative plasmids with containment circuits, and engineered live biotherapeutics—that may complement or overcome current limitations. Collectively, these developments illustrate the potential of CRISPR-based antimicrobials to augment traditional therapies through precise gene-level suppression of carbapenem resistance.
Keywords: antimicrobial resistance, bacteriophage delivery, Carbapenem resistance, Cas13a/Cas13d RNA targeting, Cas9 plasmid curing, conjugative CRISPR vectors, CRISPR–Cas systems, horizontal gene transfer
Received: 14 Oct 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Tsolakidou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Pandora Jim Tsolakidou
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