Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication

Phages have been shown to use diverse strategies to commandeer bacterial host cell metabolism during infection. However, for many of the physiological changes in bacteria during infection, it is often unclear if they are part of a bacterial response to infection or if they are actively driven by the phage itself. Here, we identify two phage proteins that promote efficient phage replication by reprogramming host amino acid metabolism. These proteins, Eht1 and Eht2, are expressed early in the infection cycle and increase the levels of key amino acids and the arginine-derived polyamine putrescine. This provides a fitness advantage as these metabolites are important for phage replication and are often depleted during infection. We provide evidence that Eht1 and Eht2 alter the expression of bacterial host metabolic genes, and their activities may impinge on metabolism-related signaling processes. This work provides new insight into how phages ensure access to essential host resources during infection and the competitive advantage this provides.