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Fradet, O.

Publications and source records attributed to Fradet, O..

2 recordsLinked to original sources

The ambivalent effect of spatial structure on the spread of cooperative anti-CRISPR phages

Some phages have evolved the ability to cooperate to evade the immunity triggered by their bacterial host. A first exposure to the phage may weaken the host defences and allow later infections to be successful. Because this cooperation requires sequential infections, the phage can invade the host population only if its initial density is sufficiently high in a well-mixed environment. However, most natural bacterial populations are spatially structured. Could spatial structure create more favourable conditions for viral spread? Here we study the effect of spatial structure on the dynamics of cooperative anti-CRISPR (Acr) phages spreading in a population of CRISPR-Cas resistant Pseudomonas aeruginosa bacteria. We show experimentally that spatial structure does not always promote the spread of Acr-phages. In particular, the effect of spatial structure is modulated by the efficacy of the bacterial hosts CRISPR-Cas resistance and by the efficacy of the phage Acr protein. These results are discussed in the light of a mathematical model we developed to describe the spread of the phage. The model allows us to understand the ambivalent effects of spatial structure via its effects on the reproduction and on the persistence of the phage. More generally, we find that spatial structure can have opposite effects on the epidemiological dynamics of the phage, depending on the properties of the Acr protein encoded by the phage. This joint experimental and theoretical work yields a deeper understanding of the spatial dynamics of cooperative strategies in phages.

microbiology↗

Exploitation of the cooperative behaviours of anti-CRISPR phages

Many bacteria encode CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-associated) adaptive immune systems to protect themselves against their viruses (phages)1. To overcome resistance, phages have evolved anti-CRISPR proteins (Acr), which naturally vary in their potency to suppress the host immune system and avoid phage extinction2,3,4,5. However, these Acr-phages need to cooperate in order to overcome CRISPR-based resistance4,5: while many initial infections by Acr-phages are unsuccessful, they nonetheless lead to the production of Acr proteins, which generate immunosuppressed cells that can be successfully exploited by other Acr-phages in the population4,5. Here we test the prediction that phages lacking acr genes (Acr-negative phages) may exploit this cooperative behaviour6. We demonstrate that Acr-negative phages can indeed benefit from the presence of Acr-positive phages during pairwise competitions, but the extent of this exploitation depends on the potency of the Acr protein. Specifically, \"strong\" Acr proteins are more exploitable and benefit both phage types, whereas \"weak\" Acr proteins predominantly benefit Acr-positive phages only and therefore provide a greater fitness advantage during competition with Acr-negative phages. This work further helps to explain what defines the strength of an Acr protein, how selection acts on different Acr types in a phage community context, and how this can shape the dynamics of phage populations in natural communities.

microbiology↗