Roseobacters And Their Infecting Phage As Models For Understanding The Fate Of Virus-Mediated Cell Lysis In Marine Systems

It is well established that during phage infection, the host cell provides metabolic resources for virus replication. However, we know relatively little of how the infection process affects host metabolism at a global level. Our specific objective is to provide an understanding of how host metabolism is altered during phage infection and also to provide a framework for understanding how the infection process can alter the composition of cellular constituents that are released into the environment and are available for consumption by uninfected microbes. We hypothesize that although phage infection results in a global change in metabolite concentrations in a cell, pathways involved in nucleotide biosynthesis, nitrogen metabolism and intermediates in cell wall biosynthesis are especially affected by phage infection. We selected a representative member of the Roseobacter lineage of marine bacteria, Sulfitobacter sp. CB2047, as an environmentally relevant model for this work. Using a targeted tandem liquid chromatography and mass spectrometry approach, we determined the metabolite profile and the flux of selected metabolites of phage infected and uninfected CB2047 over an infection cycle. Our results indicate that phage infected cells are metabolically hyperactive compared to uninfected cells and that as a result of phage infection the host resources are redirected from energy production to the production of  new phage particles. From our results we conclude that there is a metabolome remodeling during phage infection that affects nitrogen metabolism, amino acid metabolism, DNA synthesis and intermediates in call wall biosynthesis all of which are required for effective phage replication.