Weberviruses are gut-associated phages that infect Klebsiella spp

Dawson, Samuel J. T., Shibu, Preetha, Garnett, Sara, Newberry, Fiona, Brook, Thomas C., Tijani, Tobi, Kujawska, Magdalena, Hall, Lindsay J., McCartney, Anne L., Negus, David and Hoyles, Lesley (2025) Weberviruses are gut-associated phages that infect Klebsiella spp. FEMS Microbiology Ecology, 101 (5). ISSN 0168-6496

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Abstract

Weberviruses are bacteriophages (phages) that can infect and lyse clinically relevant, multidrug-resistant (MDR) strains of Klebsiella. They are an attractive therapeutic option to tackle Klebsiella infections due to their high burst sizes, long shelf life, and associated depolymerases. In this study, we isolated and characterized seven new lytic phages and compared their genomes with those of their closest relatives. Gene-sharing network, ViPTree proteome, and terL gene-sequence-based analyses incorporating all publicly available webervirus genomes [n = 258 from isolates, n = 65 from metagenome-assembled genome (MAG) datasets] confirmed the seven phages as members of the genus Webervirus and identified a novel genus (Defiantjazzvirus) within the family Drexlerviridae. Using our curated database of 265 isolated phage genomes and 65 MAGs (n = 330 total), we found that weberviruses are distributed globally and primarily associated with samples originating from the gut: sewage (154/330, 47%), wastewater (83/330, 25%), and human faeces (66/330, 20%). We identified three distinct clusters of potential depolymerases encoded within the 330 genomes. Due to their global distribution, frequency of isolation and lytic activity against the MDR clinical Klebsiella strains used in this study, we conclude that weberviruses and their depolymerases show promise for development as therapeutic agents against Klebsiella spp.

Item Type: Article
Additional Information: Data availability statement: The sequences for the seven new phage genomes described herein have been deposited in DDBJ/ENA/GenBank under accession numbers OM065837-OM065843. The genome sequences of bacteria described herein have been deposited under BioProject PRJNA917129. All supplementary material is available from https://figshare.com/projects/Weberviruses_are_gut-associated_phages_that_infect_Klebsiella_spp_/128516. Funding information: Imperial Health Charity is thanked for contributing to registration fees for the Professional Doctorate studies of P.S. P.S. was in receipt of an IBMS Research Grant (project title ‘Isolation of lytic bacteriophages active against antibiotic-resistant Klebsiella pneumoniae’). This work used computing resources provided by UK Med-Bio (Medical Research Council grant number MR/L01632X/1) and the Research Contingency Fund of the Department of Biosciences, Nottingham Trent University. S.J.T.D. was funded by Nottingham Trent University. S.G. completed this work as part of an MRes degree at NTU. L.J.H. is supported by Wellcome Trust Investigator Awards no. [220876/Z/20/Z].
Uncontrolled Keywords: comparative genomics,environment,klebsiella pneumoniae,metagenome-assembled genomes,microbiota,microbiology,ecology,applied microbiology and biotechnology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 11 Jun 2025 13:30
Last Modified: 20 Jun 2025 00:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/99466
DOI: 10.1093/femsec/fiaf043

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