Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity

Abstract

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.\n\nHighlightsO_LIBacteria with CRISPR immunity remain partially resistant to Acr-phage\nC_LIO_LISequentially infecting Acr phages cooperate to overcome CRISPR resistance\nC_LIO_LIAcr-phage epidemiology depends on the initial phage density\nC_LIO_LICRISPR resistant bacteria can drive Acr phages extinct\nC_LI\n\neTOC blurbSome 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.