Abstract
SummarySome 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 blocking 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 toward higher initial phage densities. Collectively, these data help elucidate how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.
Highlights
Bacteriophages are highly abundant in virtually all environments and are thought to play a key role in shaping the ecology and evolution of their bacterial hosts (Koskella and Brockhurst, 2014; Weitz, 2015; van Houte et al, 2016a)
CRISPR-Cas Confers Partial Immunity to Acr-Phages To investigate the consequences of the partial resistance of CRISPR immune bacteria against Acr-phages (Figure S1A), we expressed AcrIF1 and AcrIF4 in an isogenic phage DMS3mvir background, which lacks an endogenous AcrIF but is closely related to both parental phages (91% and 80% pairwise sequence identity, respectively)
Consistent with previous observations (Bondy-Denomy et al, 2013), efficiency of plaquing (EOP) assays with DMS3mvirAcrIF1 and DMS3mvir-AcrIF4 confirmed partial immunity of P. aeruginosa strain UCBPP-PA14 (WT PA14) hosts with CRISPR resistance to these Acr-phages and demonstrated that Acrs differ in their ability to block CRISPR resistance, with AcrIF1 being a more potent suppressor of CRISPR resistance than AcrIF4 (Figure 1A)
Summary
Bacteriophages (phages) are highly abundant in virtually all environments and are thought to play a key role in shaping the ecology and evolution of their bacterial hosts (Koskella and Brockhurst, 2014; Weitz, 2015; van Houte et al, 2016a). The observation that phages persist in the environment in spite of these host defenses is likely due to a combination of ecological and evolutionary processes (Thompson, 2005). Approximately half of the sequenced bacterial genomes encode CRISPR-Cas immune systems (Grissa et al, 2007; Makarova et al, 2015), and in response, many phages have evolved anti-CRISPR (acr) genes that inhibit the CRISPR immune response (Bondy-Denomy et al, 2013; Pawluk et al, 2014; Pawluk et al, 2016a). The conditions and extent to which these immunosuppressive genes allow phages to persist in the face of bacteria with CRISPR resistance have remained unclear
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