Genomes from Uncultivated Pelagiphages Reveal Multiple Phylogenetic Clades Exhibiting Extensive Auxiliary Metabolic Genes and Cross-Family Multigene Transfers

Wittmers, Fabian; Needham, David M.; Hehenberger, Elisabeth; Giovannoni, Stephen J.; Worden, Alexandra Z.

doi:10.1128/msystems.01522-21

Cited by 12 publications

(8 citation statements)

References 72 publications

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“…Phage satellites have also been suggested to contribute to broader host ranges [90,91]. Furthermore, the transfer of potentially beneficial metabolic genes from temperate phages to their bacterial hosts may enhance host competitiveness and contribute to overall microbiota changes [92,93]. These findings align with recent research demonstrating the significant influence of nutritional and host environments on the community ecology [94], suggesting that cascading events initiated by FVT could catalyze changes in the host environment.…”

Section: Discussionsupporting

confidence: 74%

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments

Rasmussen

Förster

Larsen

et al. 2023

Preprint

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Fecal microbiota transplantation (FMT) from a healthy donor to recurrent C. difficile infection (CDI) patients has proven efficient in curing the disease, possibly through bacteriophage-mediated (phages) modulation of the gut microbiome landscape. Fecal virome transplantation (FVT, sterile filtrated donor feces) has also been shown efficient for treating the disease. FVT has the advantage over FMT that no bacteria are transferred, but FVT does not exclude the risk of transferring eukaryotic viruses. We aimed to develop methodologies to obtain safer FVT by removing and/or inactivating eukaryotic viruses, while maintaining an active phage community. Donor feces were used as inoculum for a chemostat-fermentation to remove eukaryotic viruses by dilution (FVT-ChP). FVT solutions underwent solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT) and pyronin-Y treatment to block the replication of RNA-viruses (FVT-PyT). The efficacy of these treatments was assessed in a CDI mouse model and compared with untreated FVT (FVT-UnT), FMT, and saline-treatment as controls. Intriguingly, 8/8 mice receiving FVT-SDT did not reach the humane endpoints until planned euthanization and expressed limited symptoms of CDI. While 5/7 saline treated mice reached the humane endpoint. Compared to the saline treatment, lower C. difficile abundance (p<0.005) in the FVT-SDT-treated mice suggested that the intervention had hampered C. difficile colonization. The mice receiving FVT-ChP and FVT-UnT tended to express alleviated CDI symptoms compared to the saline control. This proof-of-concept study may constitute the initial step of developing therapeutic tools that targets a broad spectrum of gut-related diseases and thereby substituting FMT with a safer phage-mediated therapies.

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Section: Discussionsupporting

confidence: 74%

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments

Rasmussen

Förster

Larsen

et al. 2023

Preprint

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“…Phage satellites have, amongst other, been suggested to contribute to broader host ranges 86,87 . Also, the transfer of potentially beneficial metabolic genes from temperate phages to their bacterial hosts [88][89][90][91] , may enhance host competitiveness and contribute to overall GM changes. These findings align with recent research demonstrating how metabolic functions and bacterial interaction networks were context-dependent of variables like nutrition, host environment, and bacterial compositions 92 , supporting the hypothesis that cascading events initiated by FVT could catalyze GM modulating effects.…”

Section: Discussionmentioning

confidence: 99%

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

Mao,

Larsen,

Zachariassen

et al. 2024

Nat Commun

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Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.

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“…Predicted proteins belonging to significant differentially abundant gene categories between seasonal and non-seasonal chronotypes were analysed. To determine whether the enrichment of potential AMGs reflects a particular adaptation of a majority of seasonal pelagiphages (enriched in co-ocurring ferrochelatase and 2-OG(FeII) oxygenases) [66] or a broader observation, we analysed together both the vOTU proteins and those annotated from known pelagiphage genomes. Genomes from cultured and curated metagenome assembled pelagiphages [66][67][68][69][70][71] were re-annotated as previously described to standardise functional prediction.…”

Section: Phylogenetic Analysismentioning

confidence: 99%

“…To determine whether the enrichment of potential AMGs reflects a particular adaptation of a majority of seasonal pelagiphages (enriched in co-ocurring ferrochelatase and 2-OG(FeII) oxygenases) [66] or a broader observation, we analysed together both the vOTU proteins and those annotated from known pelagiphage genomes. Genomes from cultured and curated metagenome assembled pelagiphages [66][67][68][69][70][71] were re-annotated as previously described to standardise functional prediction. Predicted proteins annotated as ferrochelatase, primase, or 2-OG(FeII) oxygenases were retrieved and aligned together using t-coffee v12.0 [72].…”

Section: Phylogenetic Analysismentioning

confidence: 99%

Viral chronotypes and their role in shaping seasonal viral dynamics in the Western English Channel

Bolaños,

Michelsen,

Temperton

2024

Preprint

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Marine viruses are key players of ocean biogeochemistry, profoundly influencing microbial community ecology and evolution. Despite their importance, few studies have explored the temporal dynamics of viral genome abundances in marine environments. Viral dynamics are complex, influenced by multiple factors such as host population dynamics and environmental conditions. To disentangle the complexity of viral communities, we developed an unsupervised machine learning framework to classify viral genomes into "chronotypes" based on temporal abundance patterns. Analysing an inter-seasonal monthly time-series of surface viral metagenomes from the Western English Channel, we identified chronotypes and compared their functional and evolutionary profiles. Results revealed a consistent annual cycle with steep compositional changes from winter to summer and steadier transitions from summer to winter. Seasonal chronotypes were enriched in potential auxiliary metabolic genes like ferrochelatases and 2OG-Fe(II) oxygenases compared to non-seasonal types. Chronotypes clustered into four groups based on their correlation profiles with environmental parameters, primarily driven by temperature and nutrients. Viral genomes exhibited a rapid turnover of polymorphisms, akin to Red Queen dynamics. However, within seasonal chronotypes, some sequences exhibited annual polymorphism recurrence, which declined over a 16-month period, suggesting that a fraction of the seasonal viral populations evolve more slowly. Classification into chronotypes revealed viral genomic signatures linked to temporal patterns, likely reflecting metabolic adaptations to environmental fluctuations and host dynamics. This novel framework enables the identification of long-term trends in viral composition, environmental influences on genomic structure, and potential viral interactions.

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Genomes from Uncultivated Pelagiphages Reveal Multiple Phylogenetic Clades Exhibiting Extensive Auxiliary Metabolic Genes and Cross-Family Multigene Transfers

Abstract: One of the most abundant and diverse marine bacterial groups is Pelagibacter . Phages have roles in shaping Pelagibacter ecology; however, several Pelagiphage lineages are represented by only a few genomes.

Cited by 12 publications

References 72 publications

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

Viral chronotypes and their role in shaping seasonal viral dynamics in the Western English Channel

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