BBSRC-NSF/BIO:Collaborative Research: Phage host range evolution in spatially structured microbiomes

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Bacteriophages, the viral parasites of bacteria, are major agents of bacterial death in microbial communities or microbiomes. Previous work has shown that phage host range, the type of bacteria a given phage can successfully infect, can evolve rapidly. This evolution alters the impact that phage have on the composition and function of microbial communities. However, this previous work has focused on bacteria growing in well-mixed conditions while many bacteria in microbiomes exist in aggregations known as biofilms. In biofilms not only is the spatial arrangement of bacteria different, but also their physiology or lifestyle. In this project, which is a collaboration between researchers at the University of Minnesota (US), Dartmouth College (US) and the University of Exeter (UK), research will pair state of the art computer simulations with cutting edge experimental approaches to develop and test theory for predicting the impact that bacteriophage have on bacterial communities. This work will improve our ability to manage microbial communities that are vital for human health, agricultural production, and industrial applications. The project will help train the next generation of scientific leaders by working with postdoctoral researchers and graduate students to carry out the research. Additionally, it will develop teaching modules to engage high school students with the power of computational biology, preparing them to drive the bio-economy of the future.Despite the abundance of phage and the prevalence of biofilm growth, little is known about the interaction between phage and biofilms. Specifically, there has been a paucity of investigation on how biofilms influence the evolution of phage host range. In addition to developing knowledge on a process that is critical to understanding microbiome behavior, the proposed work will also improve understanding of the evolution of generalist and specialist strategies more broadly. It will connect individual parasite movement to the dynamics of infection waves in heterogeneous environments. Additionally, it will quantify how host heterogeneity that arises from biotic and abiotic factors alters the evolution of parasite host range. The work will integrate a variety of models that span different length scales, with a powerful model system involving Escherichia coli and the bacteriophage T7. The research will develop and test theory to understand the impact of spatial organization, including the abundance of different hosts in a structured environment, the size of patches of hosts and the connectivity of these patches. The research will also develop and test theory to understand the consequences of bacterial matrix production, metabolic heterogeneity of hosts, and host mixing in biofilms. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.