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.
Reviewing Editor
- Blake Wiedenheft, Montana State University, United States
Publication history
- Received: April 8, 2017
- Accepted: August 7, 2017
- Accepted Manuscript published: August 17, 2017 (version 1)
- Version of Record published: August 30, 2017 (version 2)
- Version of Record updated: March 2, 2018 (version 3)
- Version of Record updated: April 4, 2018 (version 4)
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
-
- 2,863
- Page views
-
- 438
- Downloads
-
- 53
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
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 emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is alarming and demands in-depth knowledge for timely diagnosis. We performed genome-wide association analysis using 2237 clinical strains of Mtb to identify novel genetic factors that evoke drug resistance. In addition to the known direct targets, we identified for the first time, a strong association between mutations in DNA repair genes and the multidrug-resistant phenotype. To evaluate the impact of variants identified in the clinical samples in the evolution of drug resistance, we utilized knockouts and complemented strains in Mycobacterium smegmatis and Mtb. Results show that variant mutations compromised the functions of MutY and UvrB. MutY variant showed enhanced survival compared with wild-type (Rv) when the Mtb strains were subjected to multiple rounds of ex vivo antibiotic stress. In an in vivo guinea pig infection model, the MutY variant outcompeted the wild-type strain. We show that novel variant mutations in the DNA repair genes collectively compromise their functions and contribute to better survival under antibiotic/host stress conditions.
