Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes

Abstract

BackgroundViral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases.MethodsWe identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages.ResultsWe show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls.ConclusionSince IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0452-1) contains supplementary material, which is available to authorized users.

New insights into intestinal phages

“…The high abundance of temperate phages is compatible with the observation that among isolated gut bacteria, most strains are lysogens and often polylysogens, notably within the dominant Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria phyla. [30][31][32][33][34] Several metagenomic studies further suggest that the majority of intestinal bacteria carry prophages. 35,36 Yet, estimations of prophage prevalence based on genomic analyses cannot distinguish "active" prophages from "defective" ones, i.e., those that have lost the capacity to resume a lytic cycle due to mutations.…”

Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages

“…tRNA were searched with tRNAscanSE 2.0 70 . A systematic search for reverse transcriptases, frequently found in intestinal phages 18 , was conducted with hmmscan against Pfam profile PF00078, and none was found. Antibiotic resistance genes were searched using ResFam core profiles and hmmscan as indicated by the authors 47 .…”

“…Beyond coliphages, a suggestion that phages may play a role in microbiota stability came from a large virome study, which detected an increase in virome richness in Crohn's disease patients, compared to healthy subjects 17 . Furthermore, a reanalysis of this dataset focusing on the temperate phages associated with Faecalibacterium prausnitzii, a dominant bacterial member of the human microbiota which is depleted in Crohn's disease patients, suggested a negative correlation between bacterial and viral abundances for this species 18 . Such a situation may originate from massive prophage induction in a dysbiotic context.…”

The enemy from within: a prophage ofRoseburia intestinalissystematically turns lytic in the mouse gut, driving bacterial adaptation by CRISPR spacer acquisition

“…S1A). Phage genomes were annotated using RAST (Aziz et al 2008), HHPRED (Zimmermann et al 2018) and Phagonaute (Delattre et al 2016) as previously described (Cornuault et al 2018).…”

“…to establish in a stable dormant state in the infected cell. The dormant phage is called a prophage, the bacterial host a lysogen, and it is estimated that about 80% of bacteria are lysogens in the mammal's gut , Cornuault et al 2018, Kim 2018. In line with this estimation, virions from temperate phages are dominant among intestinal viruses (Reyes et al 2010, Minot et al 2011, Knowles et al 2016.…”