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Journal Article Review Epublish 1 citation

PubMed: 40176174 DOI: 10.1186/s41182-025-00728-2

Reinvigorating AMR resilience: leveraging CRISPR-Cas technology potentials to combat the 2024 WHO bacterial priority pathogens for enhanced global health security-a systematic review.

Trop Med Health 53(1):43

Authors: Olalekan John Okesanya, Mohamed Mustaf Ahmed, Jerico Bautista Ogaya, Blessing Olawunmi Amisu, Bonaventure Michael Ukoaka, Olaniyi Abideen Adigun, Emery Manirambona, Olakulehin Adebusuyi, Zhinya Kawa Othman, Olanegan Gloria Oluwakemi, Oluwaseunayo Deborah Ayando, Maria Ivy Rochelle S Tan, Nimat Bola Idris, Hassan Hakeem Kayode, Tolutope Adebimpe Oso, Musa Ahmed, M B N Kouwenhoven, Adamu Muhammad Ibrahim, Don Eliseo Lucero-Prisno

Affiliations

  • Department of Public Health and Maritime Transport, University of Thessaly, Volos, Greece.
  • Department of Medical Laboratory Science, Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria.
  • Department of Medical Laboratory Science, Chrisland University, Abeokuta, Nigeria.
  • Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia.
  • Department of Medical Technology, Institute of Health Sciences and Nursing, Far Eastern University, Manila, Philippines.
  • Center for University Research, University of Makati, Makati, Philippines.
  • Department of Medical Laboratory Services, State Hospital, Ede, Osun State, Nigeria.
  • Community and Clinical Research Division, First On-Call Initiative, Port Harcourt, Nigeria.
  • Department of Medical Laboratory Science, Nigerian Defence Academy, Kaduna, Nigeria.
  • College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
  • Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
  • Department of Pharmacy, Kurdistan Technical Institute, Sulaimani, Kurdistan Region, Iraq.
  • Department of Pharmacy, University of Ilorin, Ilorin, Nigeria.
  • Department of Public Health, Kwara State University, Malete, Nigeria.
  • Department of Nursing, University of the Philippines School of Health Sciences, Manila, Philippines.
  • Department of Public Health, Al-Hikmah University, Ilorin, Nigeria.
  • Department of Medical Laboratory Science, Oyo State Hospital Management Board, Oyo, Nigeria.
  • Department of Medical Laboratory Science, Federal Teaching Hospital, Ido-Ekiti, Nigeria.
  • Department of Physics, Xi'an Jiaotong-Liverpool University, Suzhou, China.
  • Department of Immunology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
  • Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. Research and Development Office, Biliran Province State University, Naval, Leyte, Philippines. Research and Innovation Office, Southern Leyte State University, Sogod, Southern Leyte, Philippines.

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 × 10 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.

MeSH

Genes, Clustered Regularly Interspaced Short Palindromic Repeats, Global Health, Fosfomycin, Bacteria, Carbapenems, Crispr-Cas Systems, Plasmids

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