RT Journal Article
SR Electronic
T1 Prophages are associated with extensive CRISPR-Cas auto-immunity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.02.973784
DO 10.1101/2020.03.02.973784
A1 Nobrega, Franklin L.
A1 Walinga, Hielke
A1 Dutilh, Bas E.
A1 Brouns, Stan J.J.
YR 2020
UL http://biorxiv.org/content/early/2020/08/04/2020.03.02.973784.abstract
AB 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. The mechanisms of auto-immunity evasion create tolerance to STS-targeted prophages, and contribute both to viral dissemination and bacterial diversification.Competing Interest StatementThe authors have declared no competing interest.