Prophages are associated with extensive, tolerated CRISPR-Cas auto-immunity
Prophages are associated with extensive, tolerated CRISPR-Cas auto-immunity
CRISPR–Cas systems require discriminating self from non-self DNA during adaptation and interference. Yet, multiple cases have been reported of bacteria containing self-targeting spacers (STS), i.e. CRISPR spacers targeting protospacers on the same genome. STS has been suggested to reflect potential auto-immunity as an unwanted side effect of CRISPR–Cas defense, or a regulatory mechanism for gene expression. Here we investigated the incidence, distribution, and evasion of STS in over 100 000 bacterial genomes. We found STS in all CRISPR–Cas types and in one fifth of all CRISPR-carrying bacteria. Notably, up to 40% of I-B and I-F CRISPR–Cas systems contained STS. We observed that STS-containing genomes almost always carry a prophage and that STS map to prophage regions in more than half of the cases. Despite carrying STS, genetic deterioration of CRISPR–Cas systems appears to be rare, suggesting a level of escape from the potentially deleterious effects of STS by other mechanisms such as anti-CRISPR proteins and CRISPR target mutations. We propose a scenario where it is common to acquire an STS against a prophage, and this may trigger more extensive STS buildup by primed spacer acquisition in type I systems, without detrimental autoimmunity effects as mechanisms of auto-immunity evasion create tolerance to STS-targeted prophages.
12074-12084
Luzia De Nobrega, Franklin
6532795d-88a4-4f05-9b26-6af5b8f21a0d
Walinga, Hielke
14669684-93c1-4f29-86fa-0d17fce50822
Dutilh, Bas E
8519e83d-857f-489f-9559-60a06b35ae9e
Brouns, Stan J J
b9c93a6a-120b-476b-8394-048e41d8ae79
21 November 2020
Luzia De Nobrega, Franklin
6532795d-88a4-4f05-9b26-6af5b8f21a0d
Walinga, Hielke
14669684-93c1-4f29-86fa-0d17fce50822
Dutilh, Bas E
8519e83d-857f-489f-9559-60a06b35ae9e
Brouns, Stan J J
b9c93a6a-120b-476b-8394-048e41d8ae79
Luzia De Nobrega, Franklin, Walinga, Hielke, Dutilh, Bas E and Brouns, Stan J J
(2020)
Prophages are associated with extensive, tolerated CRISPR-Cas auto-immunity.
Nucleic Acids Research, 48 (2), .
(doi:10.1093/nar/gkaa1071).
Abstract
CRISPR–Cas systems require discriminating self from non-self DNA during adaptation and interference. Yet, multiple cases have been reported of bacteria containing self-targeting spacers (STS), i.e. CRISPR spacers targeting protospacers on the same genome. STS has been suggested to reflect potential auto-immunity as an unwanted side effect of CRISPR–Cas defense, or a regulatory mechanism for gene expression. Here we investigated the incidence, distribution, and evasion of STS in over 100 000 bacterial genomes. We found STS in all CRISPR–Cas types and in one fifth of all CRISPR-carrying bacteria. Notably, up to 40% of I-B and I-F CRISPR–Cas systems contained STS. We observed that STS-containing genomes almost always carry a prophage and that STS map to prophage regions in more than half of the cases. Despite carrying STS, genetic deterioration of CRISPR–Cas systems appears to be rare, suggesting a level of escape from the potentially deleterious effects of STS by other mechanisms such as anti-CRISPR proteins and CRISPR target mutations. We propose a scenario where it is common to acquire an STS against a prophage, and this may trigger more extensive STS buildup by primed spacer acquisition in type I systems, without detrimental autoimmunity effects as mechanisms of auto-immunity evasion create tolerance to STS-targeted prophages.
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gkaa1071
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Accepted/In Press date: 22 October 2020
Published date: 21 November 2020
Identifiers
Local EPrints ID: 443088
URI: http://eprints.soton.ac.uk/id/eprint/443088
ISSN: 0305-1048
PURE UUID: ec9a59c8-bf16-4951-a88a-09a8fb1ccc20
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Date deposited: 10 Aug 2020 16:30
Last modified: 17 Mar 2024 04:02
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Author:
Hielke Walinga
Author:
Bas E Dutilh
Author:
Stan J J Brouns
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