MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut
- Institut Pasteur, France
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 6,000 interactions bridging a metagenomic assembled genomes (MAGs) and a phage sequence, allowing to study in situ phage-host ratio. Whereas three-quarter 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.
Data availability
Sequence data (raw reads, assemblies) have been deposited in the NCBI Sequence Read Archive under the BioProject number PRJNA627086.Code and additional data on MAGs, Bins, Contigs and Phages can be found at the following address https://github.com/mmarbout/HGP-Hi-C.
Article and author information
Author details
Funding
European Research Council (771813)
- Romain Koszul
Agence Nationale pour la Recherche (ANR-16-JPEC-0003-05)
- Romain Koszul
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The work involved feces samples of healthy human individuals, stored in the Institut Pasteur biobanque (library). This research receives the ethical agreement n{degree sign}N18 from Institut Pasteur (ICAReB), and through this process we dont need informed consent from the individual donors.
Copyright
© 2021, Marbouty et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,613
- views
-
- 658
- downloads
-
- 76
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut
eLife 10:e60608.
https://doi.org/10.7554/eLife.60608
Further reading
-
- Microbiology and Infectious Disease
The model Gram-negative plant pathogen Pseudomonas syringae utilises hundreds of transcription factors (TFs) to regulate its functional processes, including virulence and metabolic pathways that control its ability to infect host plants. Although the molecular mechanisms of regulators have been studied for decades, a comprehensive understanding of genome-wide TFs in Psph 1448A remains limited. Here, we investigated the binding characteristics of 170 of 301 annotated TFs through chromatin immunoprecipitation sequencing (ChIP-seq). Fifty-four TFs, 62 TFs, and 147 TFs were identified in top-level, middle-level, and bottom-level, reflecting multiple higher-order network structures and direction of information flow. More than 40,000 TF pairs were classified into 13 three-node submodules which revealed the regulatory diversity of TFs in Psph 1448A regulatory network. We found that bottom-level TFs performed high co-associated scores to their target genes. Functional categories of TFs at three levels encompassed various regulatory pathways. Three and 25 master TFs were identified to involve in virulence and metabolic regulation, respectively. Evolutionary analysis and topological modularity network revealed functional variability and various conservation of TFs in P. syringae (Psph 1448A, Pst DC3000, Pss B728a, and Psa C48). Overall, our findings demonstrated a global transcriptional regulatory network of genome-wide TFs in Psph 1448A. This knowledge can advance the development of effective treatment and prevention strategies for related infectious diseases.
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
The members of the Mycobacterium tuberculosis complex (MTBC) causing human tuberculosis comprise 10 phylogenetic lineages that differ in their geographical distribution. The human consequences of this phylogenetic diversity remain poorly understood. Here, we assessed the phenotypic properties at the host-pathogen interface of 14 clinical strains representing five major MTBC lineages. Using a human in vitro granuloma model combined with bacterial load assessment, microscopy, flow cytometry, and multiplexed-bead arrays, we observed considerable intra-lineage diversity. Yet, modern lineages were overall associated with increased growth rate and more pronounced granulomatous responses. MTBC lineages exhibited distinct propensities to accumulate triglyceride lipid droplets—a phenotype associated with dormancy—that was particularly pronounced in lineage 2 and reduced in lineage 3 strains. The most favorable granuloma responses were associated with strong CD4 and CD8 T cell activation as well as inflammatory responses mediated by CXCL9, granzyme B, and TNF. Both of which showed consistent negative correlation with bacterial proliferation across genetically distant MTBC strains of different lineages. Taken together, our data indicate that different virulence strategies and protective immune traits associate with MTBC genetic diversity at lineage and strain level.
