Exploitation of the Cooperative Behaviors of Anti-CRISPR Phages

Jan 6, 2020Cell host & microbe

Using the Teamwork of Viruses That Block CRISPR to Their Advantage

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Abstract

Acr phages may enhance the replication of Acr-negative phages by limiting bacterial resistance to the CRISPR-Cas immune system.

Acr phages cooperate to overcome bacterial immune defenses, enabling better survival of phage populations.
Interactions between Acr phages and sensitive bacteria evolve differently based on the presence of competing phages.
Acr phages help Acr-negative phages replicate on bacterial populations that have developed resistance.
The effectiveness of Acr phages is influenced by the strength of their CRISPR-Cas inhibitors.
Weaker Acrs may provide greater fitness advantages over stronger Acrs when competing with Acr-negative phages.

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Bacteriophages encoding anti-CRISPR proteins (Acrs) must cooperate to overcome phage resistance mediated by the bacterial immune system CRISPR-Cas, where the first phage blocks CRISPR-Cas immunity in order to allow a second Acr phage to successfully replicate. However, in nature, bacteria are frequently not pre-immunized, and phage populations are often not clonal, exhibiting variations in Acr presence and strength. We explored how interactions between Acr phages and initially sensitive bacteria evolve, both in the presence and absence of competing phages lacking Acrs. We find that Acr phages benefit "Acr-negative" phages by limiting the evolution of CRISPR-based resistance and helping Acr-negative phages to replicate on resistant host sub-populations. These benefits depend on the strength of CRISPR-Cas inhibitors and result in strong Acrs providing smaller fitness advantages than weaker ones when Acr phages compete with Acr-negative phages. These results indicate that different Acr types shape the evolutionary dynamics and social interactions of phage populations in natural communities.

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Exploitation of the Cooperative Behaviors of Anti-CRISPR Phages

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