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Wortelboer, K.

Publications and source records attributed to Wortelboer, K..

2 recordsLinked to original sources

Diversity-generating retroelements enable phages to expand their host range in the human gut.

Diversity-generating retroelements (DGRs) are genetic elements that use error-prone reverse transcription to hypermutate specific target genes, most often the receptor-binding proteins of phages. They are enriched in human gut viruses, where they are hypothesised to enable phages expand their host range. Yet DGR-mediated host-range expansion across bacterial species has so far only been predicted in silico and has not been examined directly within complex microbial communities. To test this hypothesis in situ, we tracked phage-host interactions in the human gut, combining bulk metagenomic, virus-like particle (VLP), and Hi-C sequencing of longitudinal faecal samples collected over a five-week period. This culture-independent approach identified 380 interactions between 97 phages and 76 bacterial hosts. Nearly a third of these phages (31 of 97) encoded a DGR, and DGR-encoding phages were more likely to interact with multiple bacterial species. Moreover, nucleotide diversity in DGR-targeted genes increased with the number of hosts a phage interacted with and was concentrated in the surface-exposed, DGR-targeted variable region of its receptor-binding proteins. Together, these results provide in situ evidence that DGRs enable phages to expand their host range in the human gut.

microbiology↗

Members of a highly widespread bacteriophage family are hallmarks of metabolic syndrome gut microbiomes

There is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members -which impact gut bacteria- of the complex gut ecosystem remain understudied. Here, we characterized gut phageome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease. MetS gut phageome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infecting Bacteroidaceae and depleted in those infecting Ruminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy phageomes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperate Ca. Heliusviridae provides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS.

microbiology↗