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Application of CRISPR-Cas System to Mitigate Superbug Infections
Ali A Rabaan1,2,3, Mona A Al Fares4, Manar Almaghaslah5
1Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
Abstract:
Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.
Insights
CRISPR-Cas gene editing, particularly base editors like ABE and CBE, offers a precise method to combat superbug infections by editing bacterial DNA. Advanced techniques aim to enhance efficacy and reduce toxicity for effective antibiotic resistance treatment.
Area of Science:
- Microbiology
- Genetics
- Biotechnology
Background:
- Multidrug-resistant bacteria (superbugs) cause fatal global infections, exacerbated by urbanization and poor sanitation.
- The CRISPR-Cas system presents a promising tool for precise genomic editing of antibiotic-resistant bacteria.
Purpose of the Study:
- To review limitations of the CRISPR-Cas system for combating superbugs.
- To explore base-editing techniques as advanced strategies to overcome CRISPR-Cas limitations.
- To highlight research on base editors' efficacy in eliminating drug-resistant microbes.
Main Methods:
- Review of CRISPR-Cas system limitations.
- Exploration of base-editing techniques, including adenine base editors (ABE) and cytidine base editors (CBE).
- Analysis of methods for precise single base pair editing without double-strand breaks (DSBs).
Main Results:
- Base editors (ABE and CBE) enable precise point mutations (e.g., G-C to A-T) without DSBs.
- These engineered Cas9 variations offer enhanced precision and reduced toxicity compared to standard CRISPR-Cas.
- Recent studies demonstrate the potential of base editors to effectively eliminate drug-resistant bacterial strains.
Conclusions:
- Advanced base-editing techniques are crucial for maximizing the potential of CRISPR-Cas in fighting antibiotic resistance.
- Base editors provide a viable strategy to precisely target and neutralize superbug genomes.
- Further development in base editing promises more effective treatments against drug-resistant infections.
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