Anne Chevallereau “Importance of bacterial defence systems in shaping the host range of phages”

The range of bacterial strains that a phage can infect primarily depends on its capacity to bind one or several specific structures at the host cell surface. Upon adsorption and genome injection, the phage lifecycle can begin. In the case of lytic phages, a series of temporally-regulated steps follow, consisting in hijacking the host metabolism, producing new phage particles and eventually lysing the host cell. Recent work suggests that phages may bind to a larger diversity of hosts than they can kill and proposed that this is likely due to the multiplicity and diversity of defence systems encoded by the host. The search for correlations between the composition of the bacterial antiphage arsenal and the level of phage resistance yielded contrasting results. We explore the contribution of bacterial defence systems in defining phage resistance profile, using two different approaches in different model systems. First, we quantitatively measure the infectivity of 9 phages on a panel of 125 clinical isolates of Pseudomonas aeruginosa, determine their ability to adsorb on each strain and compare these data to the composition of defence systems in the isolates. Second, we use a genetic approach and test how systematic knock-out of predicted defence genes affect the phage resistance phenotype in an Escherichia coli clinical isolate. Our results suggest that the contribution of defence systems to phage resistance likely depends on environmental parameters.