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Unravelling the advances of CRISPR-Cas9 as a precise antimicrobial therapy: A systematic review
Hannay Crystynah Almeida de Souza1, Pedro Panzenhagen2, Anamaria Mota Pereira Dos Santos3
1Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil; Department of Biochemistry, Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil; Graduate Program in Biochemistry (PPGBq), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, Brazil.
Abstract:
Antimicrobial resistance is a critical public health threat, compromising treatment effectiveness. The spread of resistant pathogens, facilitated by genetic variability and horizontal gene transfer, primarily through plasmids, poses significant challenges to health systems.
Objective:
This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating antimicrobial resistance.
Methods:
The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023.
Results:
The Enterobacterales family, particularly Escherichia coli, was the main focus. The resistance genes targeted were mainly associated with β-lactam antibiotics, specifically bla genes, and colistin resistance linked to the mcr-1 gene. Plasmid vectors have been the primary delivery method for the CRISPR-Cas9 system, with conjugative plasmids resensitizing bacterial strains to various antimicrobials. Other delivery methods included electroporation, phage-mediated delivery, and nanoparticles. The efficacy of the CRISPR-Cas9 system in resensitizing bacterial strains ranged from 4.7% to 100%.
Conclusions:
Despite challenges in delivery strategies and clinical application, studies integrating nanotechnology present promising approaches to overcome these limitations. This review highlights new perspectives for the clinical use of CRISPR-Cas9 as a specific and efficient antimicrobial agent, potentially replacing traditional broad-spectrum antimicrobials in the future.
Insights
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 shows promise in combating antimicrobial resistance by resensitizing bacteria. Nanotechnology integration offers potential solutions for clinical application challenges.
Area of Science:
- Molecular Biology
- Genetics
- Public Health
Background:
- Antimicrobial resistance (AMR) is a growing global health crisis.
- Resistant pathogens spread via genetic variability and horizontal gene transfer, mainly through plasmids.
- AMR compromises the effectiveness of essential treatments.
Purpose of the Study:
- To review the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating AMR.
- To explore CRISPR-Cas9 applications against specific resistance genes and bacterial families.
Main Methods:
- Systematic literature review adhering to PRISMA guidelines.
- Searches conducted on PubMed, Embase, and Scopus databases up to July 2023.
- Focus on studies targeting resistance genes in Enterobacterales, particularly E. coli.
Main Results:
- CRISPR-Cas9 primarily targeted beta-lactam resistance (bla genes) and colistin resistance (mcr-1 gene).
- Plasmid vectors were the main delivery method, successfully resensitizing bacterial strains.
- Reported efficacy of CRISPR-Cas9 in resensitization ranged from 4.7% to 100%.
Conclusions:
- CRISPR-Cas9 demonstrates potential as a specific antimicrobial agent.
- Nanotechnology-integrated delivery strategies show promise for overcoming clinical application challenges.
- Future applications may see CRISPR-Cas9 replacing traditional broad-spectrum antimicrobials.
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