CAREER: Population and evolutionary dynamics of bacteriophage-symbiont-host interactions: Development of a multi-layered model microbiome

The overarching goal of this project is to establish a tractable host-symbiont-bacteriophage system in which to interrogate the mechanisms, phenotypic outcomes, and evolutionary dynamics of multi-partner interactions. Results from this system may provide fundamental insight into how these interactions play out on larger scales, such as within the mammalian gut microbiome.

Results may also inform phage-based therapies by illuminating long-term consequences of phage administration. As the rise of antibiotic resistance threatens our ability to treat bacterial infections, interest in using bacteriophages as natural antibiotics has significantly increased. As such, this research meets the mission of the NSF in that it promotes the progress of science.

This system and the multidisciplinary nature of the experimental approach is ideal for linking teaching and research. It can be effectively integrated into multiple biology courses and tailored to scale levels of technical and conceptual complexity. Interweaving elements of this project between research and teaching courses will provide novel hands-on research experiences to a large pool of biology students.

Thus, in addition to providing insight into the biological process and outcomes of multi-partner associations, this project provides students the ability to develop research skill sets. These Broader Impacts serve the NSF mission of advancing national prosperity by training students for entry into the bioeconomy work force.

Bacteriophages are likely to have powerful impacts on the fitness and evolution of bacterial symbionts and their host organisms. However, the intra-host location of endosymbionts may shield them from phage infection or modify infection outcomes. Despite their potential significance, few studies have explored the impact of phages on host-symbiont interactions or investigated the role of the host ecosystem in mediating symbiont-phage interactions.

The goal of this project is to establish a tractable host-symbiont-phage ecosystem to interrogate the mechanisms, phenotypic outcomes, and evolutionary dynamics of these interactions. The research strategy utilizes a natural microbial symbiosis between the social amoeba Dictyostelium discoideum and Paraburkholderia bacteria. Facultative Paraburkholderia symbionts establish intracellular infections in amoeba hosts and infection characteristics vary across symbiont strains.

This project will investigate the historical impact of phages on symbiont evolution and traits by analyzing Paraburkholderia and related bacterial genomes for prophage and phage defense elements, while ongoing phage isolation from soil-based screening will illuminate relative environmental abundance and diversity of symbiont specific phages. Ultimately, Paraburkholderia infected amoeba will be exposed to phages and continuously cultured to assess the dynamics, fitness outcomes, and evolutionary trajectory of all parties by 1) quantifying population abundances and symbiont infection patterns and 2) analyzing phenotypic and genomic characteristics of evolved and ancestral isolates.

Results from this system may provide fundamental insight into how these interactions play out in other symbiosis systems and on larger scales, help inform phage-based therapeutics, and be of relevance to microbial ecology, virology, evolutionary biology, and bacterial pathogenesis.

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.