review · Tropical Medicine and Health
Antimicrobial resistance presents a critical threat to global healthcare, with low- and middle-income nations facing substantial risks. A systematic evaluation of 48 studies published between 2014 and 2024 examined how CRISPR-Cas systems can target drug-resistant bacterial pathogens listed as priorities by the World Health Organisation. Tools including CRISPR-Cas9, Cas12a, and Cas3 effectively neutralised key resistance genes that protect bacteria against critical antibiotics such as carbapenems, colistin, and vancomycin. The systems also suppressed virulence genes in pathogens like Staphylococcus aureus and Klebsiella pneumoniae. Delivery vectors, notably bacteriophages and nanoparticles, showed notable success in laboratory and animal tests, clearing resistant plasmids with up to 94 percent efficiency and re-sensitising bacteria to conventional antibiotics. In addition, CRISPR demonstrated strong utility in diagnostic tools, achieving high sensitivity and outperforming traditional detection techniques.
Treating common infections is becoming increasingly difficult as bacteria evolve defences against standard antimicrobial medicines. By reviewing how genetic tools can selectively cut out resistance mechanisms or detect dangerous strains rapidly, this work clarifies practical ways to disarm superbugs, restore the effectiveness of existing antibiotics, and strengthen tools against infectious disease outbreaks.
This research outlines applications in molecular diagnostics and therapeutic gene-editing systems targeting drug-resistant infections. Potential users include diagnostic developers, biopharmaceutical firms, and clinical laboratories. The technologies are currently in early-stage laboratory and in vivo testing, with real-world clinical use contingent upon resolving in vivo delivery, counter-resistance risks, and ethical and regulatory requirements.
AI-generated from the published abstract. Always read the original work before citing.
Abstract Background Antimicrobial resistance (AMR) poses a global health threat, particularly in low- and middle-income countries (LMICs). Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas system technology offers a promising tool to combat AMR by targeting and disabling resistance genes in WHO bacterial priority pathogens. Thus, we systematically reviewed the potential of CRISPR–Cas technology to address AMR. Methods This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted using the Scopus and PubMed databases, focusing on publications from 2014 to June 2024. Keywords included “CRISPR/Cas,” “antimicrobial resistance,” and “pathogen.” The eligibility criteria required original studies involving CRISPR/Cas systems that targeted AMR. Data were extracted from eligible studies, qualitatively synthesized, and assessed for bias using the Joanna Briggs Institute (JBI)-standardized tool. Results Data from 48 eligible studies revealed diverse CRISPR–Cas systems, including CRISPR–Cas9, CRISPR–Cas12a, and CRISPR–Cas3, targeting various AMR genes, such as blaOXA-232, blaNDM, blaCTX-M, ermB, vanA, mecA, fosA3, blaKPC, and mcr-1, which are responsible for carbapenem, cephalosporin, methicillin, macrolide, vancomycin, colistin, and fosfomycin resistance. Some studies have explored the role of CRISPR in virulence gene suppression, including enterotoxin genes, tsst1, and iutA in Staphylococcus aureus and Klebsiella pneumoniae. Delivery mechanisms include bacteriophages, nanoparticles, electro-transformation, and conjugative plasmids, which demonstrate high efficiency in vitro and in vivo. CRISPR-based diagnostic applications have demonstrated high sensitivity and specificity, with detection limits as low as 2.7 × 102 CFU/mL, significantly outperforming conventional methods. Experimental studies have reported significant reductions in resistant bacterial populations and complete suppression of the targeted strains. Engineered phagemid particles and plasmid-curing systems have been shown to eliminate IncF plasmids, cured plasmids carrying vanA, mcr-1, and blaNDM with 94% efficiency, and restore antibiotic susceptibility. Gene re-sensitization strategies have been used to restore fosfomycin susceptibility in E. coli and eliminate blaKPC-2-mediated carbapenem resistance in MDR bacteria. Whole-genome sequencing and bioinformatics tools have provided deeper insights into CRISPR-mediated defense mechanisms. Optimization strategies have significantly enhanced gene-editing efficiencies, offering a promising approach for tackling AMR in high-priority WHO pathogens. Conclusions CRISPR–Cas technology has the potential to address AMR across priority WHO pathogens. While promising, challenges in optimizing in vivo delivery, mitigating potential resistance, and navigating ethical-regulatory barriers must be addressed to facilitate clinical translation.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.1186/s41182-025-00728-2
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
