Identifying phage-bacteria interactions using a multispecies model

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The microbial communities colonizing animals are integral to animal health and development but details about what make these communities functional and stable are lacking. Bacteriophages (viruses that infect bacteria) are the numerically dominant members of animal microbiomes and they influence many properties of these communities. Bacteriophages regulate bacterial community composition by predation, transfer genetic material between host genomes, and beneficially stimulate the immune system of animals. However, our knowledge of bacteriophages is largely restricted to a limited set of lab-adapted strains and thus our understanding of their role in animal microbiomes is lacking. Bacteriophages may influence disease through ecological processes by regulating bacterial community composition and abundance or by promoting changes in the virulence of their bacterial hosts. The factors causing microbial composition to change over time are often hard to determine and empirically test because most animal microbiomes are complex and experimental intractable. We propose to utilize an important animal model system, the honey bee (Apis mellifera), to determine how ecological and evolutionary forces shape animal microbiomes. To this end, we outline two Aims that will help us characterize these forces. Aim 1: Determine how phage resistance evolution is dependent on microbial growth conditions. In this aim we will comprehensively test different parameters of growth than are likely to influence how quickly bacteria evolve resistance against bacteriophage infections. We will carefully measure the tempo of change in sets of bacteria and phages growing together. We anticipate identifying how these dynamics are impacted by growth conditions. Aim 2: Measure the impact of microbial interactions on phage resistance evolution dynamics. In this aim we expand our research to include interacting bacterial species. In most natural conditions that microbes live in they will encounter other bacteria. These interactions likely alter how bacteria respond to and evolveresistance against the bacteriophages that infect them. Our experiments will address this by co-culturing bacteria and again measuring the tempo of evolution in these systems. In both aims we adopt an integrative approach that utilizes mathematic modeling, culturing of bacteria and phages in the lab, and testing their growth in the honey bee gut. In doing so, we benefit from the strengths of each approach and increase the rigor of our results.