Phage reprogramming of <i>Pseudomonas aeruginosa</i> 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.IMPORTANCEBacterial viruses, known as phages, are abundant in all environments that are inhabited by bacteria. During the infection process, phages exploit bacterial resources, resulting in notable changes to bacterial metabolism. However, precise mechanisms underlying these changes, and if they are driven by the phage or are a generalized bacterial response to infection, remain poorly understood. We characterized two proteins in <i>Pseudomonas aeruginosa</i> phage JBD44 whose activities alter bacterial host metabolism to optimize phage replication. Our work provides insight into how phages control bacterial processes to ensure access to essential host resources during infection.