MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut.

Martial Marbouty,Romain Koszul,Agnès Thierry,Gaël A Millot

doi:10.7554/elife.60608

Martial Marbouty, Romain Koszul + Show 2 more

Open Access

https://doi.org/10.7554/elife.60608

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Abstract

Bacteriophages play important roles in regulating the intestinal human microbiota composition, dynamics, and homeostasis, and characterizing their bacterial hosts is needed to understand their impact. We applied a metagenomic Hi-C approach on 10 healthy human gut samples to unveil a large infection network encompassing more than 6000 interactions bridging a metagenomic assembled genomes (MAGs) and a phage sequence, allowing to study in situ phage-host ratio. Whereas three-quarters of these sequences likely correspond to dormant prophages, 5% exhibit a much higher coverage than their associated MAG, representing potentially actively replicating phages. We detected 17 sequences of members of the crAss-like phage family, whose hosts diversity remained until recently relatively elusive. For each of them, a unique bacterial host was identified, all belonging to different genus of Bacteroidetes. Therefore, metaHiC deciphers infection network of microbial population with a high specificity paving the way to dynamic analysis of mobile genetic elements in complex ecosystems.

Highlights

The gut hosts a complex microbial ecosystem composed of bacteria, archaea, eukaryotic microorganisms, and viruses
The regulation of the human gut microbiome is much investigated, notably the role played by mobile genetic elements, and especially the collection of viruses present in the gut, in influencing its homeostasis maintenance
We notably showed that meta3C, a proximity ligation-based approach, allows the assembly and scaffolding of dozens of nearly complete or complete phages and bacteria genomes, as well as their relationships, when applied on a single mammalian gut sample (Marbouty et al, 2017)

Summary

Introduction

The gut hosts a complex microbial ecosystem composed of bacteria, archaea, eukaryotic microorganisms, and viruses. We notably showed that meta3C, a proximity ligation-based approach, allows the assembly and scaffolding of dozens of nearly complete or complete phages and bacteria genomes, as well as their relationships, when applied on a single mammalian gut sample (Marbouty et al, 2017). These genomes and the corresponding infection network are inferred from the quantification of collision frequencies between DNA segments in the population, captured using a derivative of chromosome conformation capture (Dekker et al, 2002). Through the use of such approach to determine phage’s host target in single samples, this study can have practical consequences, notably for fecal microbiota transplantation (Chehoud et al, 2016) or phage therapy (Dufour et al, 2019; Kortright et al., 2019)

Results

Discussion

Materials and methods