Bacteriophages, the viruses that infect bacteria, are the most ubiquitous and diverse entities on Earth, infecting the vast majority of bacteria. Lytic phages that infect and kill their bacterial host cells can alter bacterial community profiles (who is there and at what density) as well as competitive dynamics among strains, with clear potential to shape host-associated microbiomes. Phages can also impact the outcome of eukaryotic disease, either directly by infecting and killing bacterial pathogens within hosts or indirectly by changing the microbiome, which is known to play a role in many plant and animal diseases. This project uses monthly sampling of pear trees from an urban environment (Berkeley city) across multiple years and large-scale genomic sequencing efforts to determine the role phages play in Fire Blight disease, an agriculturally relevant disease of many orchard species. By fully integrating undergraduate research using a peer mentoring ladder, this exploration of phage infection and community dynamics in leaf-associated bacterial microbiomes will help identify both which bacteria are naturally targeted by phages, and how these phages shape change in pathogen densities and microbiome community composition. Bacterial and phage culturing approaches will be combined with a multi-omics analysis of the pear tree microbiome to fully elucidate how phages adapt to bacteria in nature and how such adaptation impacts the microbiome in health and disease. The long-term aim is to use these data on natural phage-mediated selection to determine if and how phages can be used to reshape microbial communities and prevent disease.

The evolutionary interactions of phages and their bacterial hosts has been studied extensively in the lab, but few studies have examined these dynamics in nature. The project integrates a four module undergraduate research program with high-throughput, culture independent sequencing of both bacterial and viral communities to examine the role of phages in bacterial community turnover and disease using a novel Pear Tree disease system (Callery ‘Bradford’ pear trees infected with the agriculturally relevant pathogen Erwinia amylovora). Through the tight integration of teaching and research, the combination of culture-dependent screening and culture-independent ‘omics’ approaches will allow for tracking of bacteria-phage dynamics over both short (monthly) and long (yearly) time scales. Overall, the project aims to build an unparalleled temporal and spatial dataset on phage host range with which to examine the role of phages (both lytic and temperate) in bacterial community assembly, stability, and pathogen invasion. The project uses both classic empirical approaches to study the strength and scale of phage adaptation and new computational approaches to predict how phages shape microbial networks. The data generated will offer unprecedented insight into bacteria-phage dynamics in nature and viral host range evolution in a complex community setting. The research further develops basic understanding of plant microbiomes and viromes, and will also support the development of a new disease ecology model system that is both amenable to undergraduate training in the emerging microbiome field and unique in its potential to gain insight into virome-microbiome interactions in both health and disease.

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.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Application #
1942881
Program Officer
Michael Mishkind
Project Start
Project End
Budget Start
2020-06-01
Budget End
2025-05-31
Support Year
Fiscal Year
2019
Total Cost
$200,000
Indirect Cost
Name
University of California Berkeley
Department
Type
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94710