Facing the therapeutic impasse of antibiotics, farming systems, among which aquaculture, should consider the extraordinary resource of phages, the natural bacterial predators, for environmental friendly practices. It is, however, crucial to understand how phages can control pathogens in a sustainable and safety manner. The goal of our project is to shed light on key ecological and evolutionary processes underlying phage-bacteria dynamics in the marine environment. An oyster bacterial pathogen, V. crassostreae and its infecting phages will be used as model system to investigate the molecular bases and evolution of phage infections in nature. Based on a field approach, we will determine whether phages influence V. crassostreae dynamics in the wild by reducing bacterial density via predation and if co-evolution applies in this natural system. Combining comparative and functional genomics we will identify genes involved in the phage host range, host resistance, and phage–host coevolution. Exploring phage-vibrio interactions in culture, we will analyze whether fitness costs can constrain evolution of resistance in oyster hemolymph. We will identify vibrio virulence genes that are negatively selected by phages. In addition we will study whether phages in combination act synergistically to control V. crassostreae. Focusing on a T4-giant phage as a model, we will assess the molecular mechanisms underpinning its broad host range and decipher its potential to spread bacterial genes by horizontal gene transfer.
Expected outcomes of the proposed research. Based on a field based approach, specific aim 1 will shed light into ecological and evolutionary dynamics of V. crassostreae and our pilot study revealed that specific clones of phages and vibrio are the unit of predation and selection. Specific aim 2 will reveal phage-driven negative selection of bacterial pathogenicity. This is schematized here by a virulent vibrio which is sensitive to a phage and cytotoxic for hemocyte. Evolving phage resistance has trade off on the ability of the vibrio to evade these immune cells. Aim 2 will also reveal whether phages in combination are better than alone to infect a vibrio. Specific aim 3 will use the T4-giant phage as model to assess risk of HGT, the evolutionary history and molecular mechanisms of broad host range phage.