Detailed knowledge of functional host responses to phage infection, have been limited to few model bacteriophages mostly infecting Escherichia coli as well as the results of low throughput and increasingly antiquated methods. However, next-generation tech-niques now make it possible to explore decades of interest in how phage affect host transcription and metabolism, now re-sparked by modern therapeutic and biotechno-logical potential, as well as to ask deeper more comprehensive questions.

By performing RNA-Seq on the non-ribosomal RNA of synchronously infected cells we are able to compare host transcript data for early, middle and late transcription with six fundamentally different lytic phages. These include representatives of the N4likevirus (72kb), Phikzlikevirus (280kb), Yualikevirus (58kb), Pbunalikevirus (67kb), Phikmvlikevirus (42kb), and novel F7-like viruses (287kb) infecting P. aeruginosa PAO1.

With this technology we are also able to look at the impact of phage infection on the abundance of host transcripts and have found a number of gene features specifically targeted by the host involved in stress responses and metabolism. Interestingly, this includes the pqsABCDE operon of P. aeruginosa PAO1, which is dramatically upregu-lated across infections. This indicates that the up-regulation may result from a host mediated response as it is unlikely that so many phages with fundamentally different mechanisms for co-opting their host would specifically target the same system in the same way. As the PQS quorum sensing system has been previously demonstrated to control a stress response encouraging metabolic dormancy, and as we have found phiKMV-like phage Luz2 is only able to infect PA14 when PQS is knocked out, we feel we may have found a novel micro-colony wide phage defense system.