Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems
- Stanford University, United States
- Universidad de Murcia, Spain
- University of Otago, New Zealand
- Stanford University School of Medicine, United States
Abstract
CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an "arms race" in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.
Data availability
-
CRISPR targeting and spacer acquisition in M. mediterranea mutants, and associated environmental investigationsPublicly accessible at NCBI Sequence Read Archive (accession no. SRP103952).
-
total RNA (> 200 nt) sequencing from MMB-1 strains over-expressing RT-Cas1, Cas2, and Marme_0670 - replicate 1Publicly accessible at NCBI Sequence Read Archive (accession no. SRR2914032).
-
total RNA (> 200 nt) sequencing from MMB-1 strains over-expressing RT-Cas1, Cas2, and Marme_0670 - replicate 2Publicly accessible at NCBI Sequence Read Archive (accession no. SRR2914033).
Article and author information
Author details
Patricia Lucas-Elio
Funding
National Institutes of Health (R01-GM37706)
- Andrew Z Fire
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Silas et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,287
- views
-
- 475
- downloads
-
- 81
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems
eLife 6:e27601.
https://doi.org/10.7554/eLife.27601
Further reading
-
- Microbiology and Infectious Disease
The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.
