ArticleEvolutionary bioinformatics online2022
Investigating the Genomic Background of CRISPR-Cas Genomes for CRISPR-Based Antimicrobials.
Article in Evolutionary bioinformatics online, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Self-assembling T7 phage syringes with modular genomes for targeted delivery of penicillin against β-lactam-resistant Escherichia coli.BMC biotechnology · 2025Article
- A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models.Frontiers in molecular biosciences · 2024Article
- CRISPR-Based Gene Editing inPharmaceuticals (Basel, Switzerland) · 2023Review
- CRISPR-Cas-Docker: web-based in silico docking and machine learning-based classification of crRNAs with Cas proteins.BMC bioinformatics · 2023Article
- Three Innovations of Next-Generation Antibiotics: Evolvability, Specificity, and Non-Immunogenicity.Antibiotics (Basel, Switzerland) · 2023Review
- In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.Biology direct · 2022Article
Corrections and comments
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Authors and funding
1 author.
Funding
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Abstract
CRISPR-Cas systems are an adaptive immunity that protects prokaryotes against foreign genetic elements. Genetic templates acquired during past infection events enable DNA-interacting enzymes to recognize foreign DNA for destruction. Due to the programmability and specificity of these genetic templates, CRISPR-Cas systems are potential alternative antibiotics that can be engineered to self-target antimicrobial resistance genes on the chromosome or plasmid. However, several fundamental questions remain to repurpose these tools against drug-resistant bacteria. For endogenous CRISPR-Cas self-targeting, antimicrobial resistance genes and functional CRISPR-Cas systems have to co-occur in the target cell. Furthermore, these tools have to outplay DNA repair pathways that respond to the nuclease activities of Cas proteins, even for exogenous CRISPR-Cas delivery. Here, we conduct a comprehensive survey of CRISPR-Cas genomes. First, we address the co-occurrence of CRISPR-Cas systems and antimicrobial resistance genes in the CRISPR-Cas genomes. We show that the average number of these genes varies greatly by the CRISPR-Cas type, and some CRISPR-Cas types (IE and IIIA) have over 20 genes per genome. Next, we investigate the DNA repair pathways of these CRISPR-Cas genomes, revealing that the diversity and frequency of these pathways differ by the CRISPR-Cas type. The interplay between CRISPR-Cas systems and DNA repair pathways is essential for the acquisition of new spacers in CRISPR arrays. We conduct simulation studies to demonstrate that the efficiency of these DNA repair pathways may be inferred from the time-series patterns in the RNA structure of CRISPR repeats. This bioinformatic survey of CRISPR-Cas genomes elucidates the necessity to consider multifaceted interactions between different genes and systems, to design effective CRISPR-based antimicrobials that can specifically target drug-resistant bacteria in natural microbial communities.
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