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Weberviruses are gut-associated phages that infect Klebsiella spp
Samuel J T Dawson1, Preetha Shibu2, Sara Garnett1
1Department of Biosciences, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom.
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.
Insights
Weberviruses, phages targeting multidrug-resistant Klebsiella, show therapeutic potential. Their global distribution and lytic activity against Klebsiella spp. highlight their promise for treating infections.
Area of Science:
- Microbiology
- Virology
- Genomics
Background:
- Weberviruses are bacteriophages (phages) capable of infecting and lysing multidrug-resistant (MDR) Klebsiella strains.
- Phage therapy presents an attractive alternative for combating Klebsiella infections due to phage characteristics like high burst sizes, stability, and depolymerases.
Purpose of the Study:
- To isolate and characterize novel lytic phages.
- To compare the genomes of newly isolated phages with existing Webervirus relatives.
- To investigate the global distribution and potential therapeutic applications of weberviruses.
Main Methods:
- Isolation and characterization of seven new lytic phages.
- Genomic comparison using gene-sharing networks, ViPTree proteome analysis, and terL gene sequencing.
- Analysis of a curated database of 330 Webervirus genomes (265 isolates, 65 MAGs).
Main Results:
- Seven novel phages were confirmed as members of the genus Webervirus.
- A new genus, Defiantjazzvirus, was identified within the Drexlerviridae family.
- Weberviruses are globally distributed, predominantly found in gut-associated environments (sewage, wastewater, feces).
- Three distinct clusters of depolymerase genes were identified within the webervirus genomes.
Conclusions:
- Weberviruses exhibit global distribution and significant lytic activity against clinical MDR Klebsiella strains.
- The identified depolymerases and the phages themselves hold promise as therapeutic agents for Klebsiella infections.
- This study expands the understanding of Webervirus diversity and ecological distribution.
