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Sensitizing pathogens to antibiotics using the CRISPR-Cas system
Moran Goren1, Ido Yosef1, Udi Qimron1
1Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Abstract:
The extensive use of antibiotics over the last century has resulted in a significant artificial selection pressure for antibiotic-resistant pathogens to evolve. Various strategies to fight these pathogens have been introduced including new antibiotics, naturally-derived enzymes/peptides that specifically target pathogens and bacteriophages that lyse these pathogens. A new tool has recently been introduced in the fight against drug-resistant pathogens-the prokaryotic defense mechanism-clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system. The CRISPR-Cas system acts as a nuclease that can be guided to cleave any target DNA, allowing sophisticated, yet feasible, manipulations of pathogens. Here, we review pioneering studies that use the CRISPR-Cas system to specifically edit bacterial populations, eliminate their resistance genes and combine these two strategies in order to produce an artificial selection pressure for antibiotic-sensitive pathogens. We suggest that intelligent design of this system, along with efficient delivery tools into pathogens, may significantly reduce the threat of antibiotic-resistant pathogens.
Insights
The clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system offers a novel approach to combat antibiotic-resistant pathogens by editing bacterial populations and eliminating resistance genes. This technology may significantly reduce the threat of drug-resistant bacteria.
Area of Science:
- Microbiology
- Genetics
- Biotechnology
Background:
- Antibiotic resistance is a growing global health threat driven by extensive antibiotic use.
- Existing strategies include new antibiotics, antimicrobial peptides, and bacteriophages.
- The clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system is a novel prokaryotic defense mechanism.
Purpose of the Study:
- To review studies utilizing the CRISPR-Cas system against antibiotic-resistant pathogens.
- To explore CRISPR-Cas applications in editing bacterial populations and eliminating resistance genes.
- To assess the potential of CRISPR-Cas in creating selection pressure for antibiotic-sensitive bacteria.
Main Methods:
- Review of pioneering studies on CRISPR-Cas system applications in bacterial manipulation.
- Analysis of strategies for specific DNA cleavage and gene editing in pathogens.
- Examination of methods for delivering CRISPR-Cas tools into bacterial populations.
Main Results:
- The CRISPR-Cas system can be guided to cleave specific DNA sequences in pathogens.
- Studies demonstrate the elimination of antibiotic resistance genes using CRISPR-Cas.
- Combining population editing and gene elimination creates artificial selection for antibiotic sensitivity.
Conclusions:
- The CRISPR-Cas system presents a sophisticated tool for combating drug-resistant pathogens.
- Intelligent design and efficient delivery are crucial for maximizing CRISPR-Cas efficacy.
- This technology holds significant potential to reduce the threat of antibiotic resistance.