Extended genomic analyses of the broad-host-range phages vB_KmiM-2Di and vB_KmiM-4Dii reveal slopekviruses have highly conserved genomes

Thomas Smith-Zaitlik, Preetha Shibu, Anne L. McCartney, Geoffrey Foster, Lesley Hoyles, David Negus

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Abstract

High levels of antimicrobial resistance among members of the Klebsiella oxytoca complex (KoC) have led to renewed interest in the use of bacteriophage (phage) therapy to tackle infections caused by these bacteria. In this study we characterized two lytic phages, vB_KmiM-2Di and vB_KmiM-4Dii, that were isolated from sewage water against two GES-5-positive Klebsiella michiganensis strains (PS_Koxy2 and PS_Koxy4, respectively). ViPTree analysis showed both phages belonged to the genus Slopekvirus. rpoB gene-based sequence analysis of 108 presumptive K. oxytoca isolates (n=59 clinical, n=49 veterinary) found K. michiganensis to be more prevalent (46 % clinical and 43 % veterinary, respectively) than K. oxytoca (40 % clinical and 6 % veterinary, respectively). Host range analysis against these 108 isolates found both vB_KmiM-2Di and vB_KmiM-4Dii showed broad lytic activity against KoC species. Several hypothetical homing endonuclease genes were encoded within the genomes of both phages, which may contribute to their broad host range. Differences in the tail fibre protein may explain the non-identical host range of the two phages. Pangenome analysis of 24 slopekviruses found that genomes within this genus are highly conserved, with more than 50 % of all predicted coding sequences representing core genes at ≥95 % identity and ≥70 % coverage. Given their broad host ranges, our results suggest vB_KmiM-2Di and vB_KmiM-4Dii represent attractive potential therapeutics. In addition, current recommendations for phage-based pangenome analyses may require revision.

Original languageEnglish
Article number001247
JournalMicrobiology
Volume168
Issue number9
Early online date26 Sep 2022
DOIs
Publication statusFirst published - 26 Sep 2022

Keywords

  • homing endonuclease
  • Klebsiella oxytoca complex
  • lytic phage
  • myovirus
  • pangenome
  • phage diversity
  • Slopekvirus
  • Water
  • Genome, Viral
  • Host Specificity
  • Genomics/methods
  • Anti-Infective Agents
  • Bacteriophages/genetics
  • Sewage
  • Endonucleases

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