Prophages are associated with extensive CRISPR-Cas auto-immunity

Journal Article (2020)
Author(s)

Franklin L. Luzia de Nobrega (TU Delft - BN/Stan Brouns Lab, Kavli institute of nanoscience Delft)

Hielke Walinga (Kavli institute of nanoscience Delft, Student TU Delft)

Bas E. Dutilh (Universiteit Utrecht)

S.J.J. Brouns (TU Delft - BN/Stan Brouns Lab, Kavli institute of nanoscience Delft)

Research Group
BN/Stan Brouns Lab
Copyright
© 2020 F. Luzia de Nobrega, Hielke Walinga, Bas E. Dutilh, S.J.J. Brouns
DOI related publication
https://doi.org/10.1093/nar/gkaa1071
More Info
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Publication Year
2020
Language
English
Copyright
© 2020 F. Luzia de Nobrega, Hielke Walinga, Bas E. Dutilh, S.J.J. Brouns
Research Group
BN/Stan Brouns Lab
Issue number
21
Volume number
48
Pages (from-to)
12074-12084
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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.