Marine viruses exploit their host's two-component regulatory system in response to resource limitation

Phosphorus (P) availability, which often limits productivity in marine ecosystems, shapes the P-acquisition gene content of the marine cyanobacteria Prochlorococcus [1-4] and its viruses (cyanophages). As in other bacteria, in Prochlorococcus these genes are regulated by the PhoR/PhoB two-component regulatory system that is used to sense and respond to P availability and is typical of signal transduction systems found in diverse organisms. Replication of cyanophage genomes requires a significant amount of P, and therefore these phages could gain a fitness advantage by influencing host P acquisition in P-limited environments. Here we show that the transcription of a phage-encoded high-affinity phosphate-binding protein gene (pstS) and alkaline phosphatase gene (phoA)-both of which have host orthologs-is elevated when the phages are infecting host cells that are P starved, relative to P-replete control cells. We further show that the phage versions of these genes are regulated by the host's PhoR/PhoB system. This not only extends this fundamental signaling mechanism to viruses but is also the first example of regulation of lytic phage genes by nutrient limitation in the host. As such, it reveals an important new dimension of the intimate coevolution of phage, host, and environment in the world's oceans.