December 14, 2023
Research Highlight

Direct Detection of Phage-Host Interactions in Soils

First application of high-throughput chromosome conformation capture (Hi-C) metagenome sequencing to soil to capture phage-host interactions at the time of sampling

An image of soil, bacteria, and phages

An image of the connections between soil, bacteria, and phages.

(Composite image by Shannon Colson | Pacific Northwest National Laboratory)

The Science                               

Bacteriophages, which are viruses that infect bacteria, are quite common in soil ecosystems. However, a significant portion of these phages remains unidentified, and the bacteria they target are a mystery. In this study, researchers employed advanced technology, called high-throughput chromosome conformation capture (Hi-C), to directly investigate the relationships between phages and their bacterial hosts in soils with varying moisture levels. Findings revealed that phages in dry soil exhibited lower activity compared to those in wet soil, and they specifically targeted bacterial hosts capable of surviving and thriving in dry conditions. Some of these identified bacterial hosts appeared to play keystone species roles in the bacterial community. This research offers experimental evidence that phages can influence the dynamics of bacterial populations as a response to changes in soil moisture and shed light on the complex interactions within soil ecosystems.

The Impact

This study marks a significant advancement in the use of Hi-C sequencing within soil environments. It allows researchers to observe and record the ongoing viral infections and identify the precise interactions between viruses and their hosts. Notably, this offers experimental evidence of viral generalists, a concept that was previously only predicted through bioinformatics. Additionally, by combining Hi-C with other DNA and RNA sequencing techniques, scientists at Pacific Northwest National Laboratory (PNNL) gained fresh perspectives on how soil drying influences the relationships between phages and their hosts, which has downstream effects on the interactions within the bacterial community.


In soil ecosystems, phages that infect bacteria are numerous but remain poorly understood in terms of their effects on the soil's microbial community when environmental conditions change. This study harnessed advanced Hi-C technology to directly observe the connections between phages and their bacterial hosts within soil.

Soil samples were collected before and after a two-week incubation period, which simulated the natural drying process that occurs in the field. To identify the interactions between phages and their hosts, the PNNL employed Hi-C, which involves chemically linking the DNA molecules of phages and their bacterial hosts that are in the same cell.

Furthermore, the researchers used paired metagenomes and metatranscriptomes generated by the Department of Energy (DOE) Joint Genome Institute through the Facilities Integrating Collaborations for User Science, or FICUS program, to examine the composition of phage and bacterial communities and their potential activities. This investigation revealed that some of the key species within the bacterial community could also serve as hosts for phages.

Researchers observed that the frequency of phage infections per host population had a significant negative correlation with the abundance of the hosts in the soil prior to the drying process. However, after the soil had dried the phages were less active, but seemed to selectively target hosts with advantageous traits. Collectively, these findings provide evidence of how phages can influence the dynamics of bacterial populations in response to changing levels of soil moisture.

PNNL Contact

Kirsten S Hofmockel, Pacific Northwest National Laboratory,

Ruonan Wu, Pacific Northwest National Laboratory,


This program is supported by the DOE, Office of Science, through the Genomic Science Program, Biological and Environmental Research program. A portion of this research was performed under the FICUS program and used resources at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at PNNL and the Joint Genome Institute (JGI), also a DOE Office of Science user facility sponsored by the Biological and Environmental Research program. Metatranscriptomic data was generated at JGI. PNNL is a multiprogram national laboratory operated by Battelle for DOE.

Published: December 14, 2023

Wu, R., M. R. Davison, W. C. Nelson, M. L. Smith, M. S. Lipton, J. K. Jansson, R. S. McClure, J. E. McDermott, and K. S. Hofmockel. 2023. “Hi-C metagenome sequencing reveals soil phage-host interactions.” Nat Commun 14, 7666.