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Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity

Mariann Landsberger, Sylvain Gandon, Sean Meaden, Hélène Chabas, Angus Buckling, Edze R. Westra, Stineke van Houte
doi: https://doi.org/10.1101/279026
Mariann Landsberger
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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Sylvain Gandon
2CEFE UMR 5175, CNRS Université de Montpellier Université Paul-Valéry Montpellier EPHE, 34293 Montpellier Cedex 5, France
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Sean Meaden
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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Hélène Chabas
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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Angus Buckling
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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Edze R. Westra
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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  • For correspondence: westra.edze@gmail.com vanhoute.stineke@gmail.com
Stineke van Houte
1ESI and CEC, Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 9EZ, UK
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  • For correspondence: westra.edze@gmail.com vanhoute.stineke@gmail.com
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Summary

Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage taking down the host CRISPR-Cas immune system to allow a second Acr- phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points towards higher phage densities. Collectively these data help to understand how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.

Highlights

  • Bacteria with CRISPR immunity remain partially resistant to Acr-phage

  • Sequentially infecting Acr phages cooperate to overcome CRISPR resistance

  • Acr-phage epidemiology depends on the initial phage density

  • CRISPR resistant bacteria can drive Acr phages extinct

eTOC blurb Some phages encode Acr proteins that block bacterial CRISPR-Cas immune systems. Although CRISPR-Cas can clear the first infection, this Acr-phage still suppresses the host immune system, which can be exploited by other Acr-phages. This is critical for Acr-phage amplification, but this “cooperation” only works beyond a critical Acr-phage density threshold.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 08, 2018.
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Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity
Mariann Landsberger, Sylvain Gandon, Sean Meaden, Hélène Chabas, Angus Buckling, Edze R. Westra, Stineke van Houte
bioRxiv 279026; doi: https://doi.org/10.1101/279026
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Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity
Mariann Landsberger, Sylvain Gandon, Sean Meaden, Hélène Chabas, Angus Buckling, Edze R. Westra, Stineke van Houte
bioRxiv 279026; doi: https://doi.org/10.1101/279026

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