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Host-encoded DNA methyltransferases modify the epigenome and host tropism of invading phages

Michiko Takahashi1, Satoshi Hiraoka2, Yuki Matsumoto3

  • 1Department of Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.

Iscience
|April 17, 2025
PubMed

Insights

Phages adapt to bacteria by acquiring DNA methylation patterns from their hosts. This study shows adapted phages share methylation motifs with their most recent bacterial host, impacting phage tropism and microbial ecology.

Area of Science:

  • Microbiology
  • Epigenetics
  • Virology

Background:

  • Restriction-modification (RM) systems are bacterial defenses against phages.
  • Phages can adapt to RM systems by acquiring host DNA methylation.
  • Previous studies hypothesized but did not directly compare phage and host methylomes.

Purpose of the Study:

  • To investigate the epigenetic landscape of phages adapted to bacterial hosts.
  • To compare the methylomes of adapted phages with their hosts.
  • To understand how phage DNA methylation influences host tropism and adaptation.

Main Methods:

  • Utilized a multistage infection system with the broad host-range phage KHP30T and three *Helicobacter pylori* strains.
  • Employed single-molecule real-time (SMRT) sequencing to analyze phage methylomes.
  • Quantified phage titers to assess host tropism changes.

Main Results:

  • Adapted phages exhibited significantly higher titers against their most recently infected *H. pylori* strain.
  • Single-molecule real-time sequencing revealed that methylated motifs in adapted phages predominantly matched those of their recent host.
  • Demonstrated a correlation between phage DNA methylation and host tropism.

Conclusions:

  • Phage adaptation to bacterial hosts involves acquiring host DNA methylation patterns.
  • Epigenetic interactions between phages and hosts are crucial for phage tropism and adaptation.
  • Findings have significant implications for understanding phage-host dynamics in microbial ecology.
Keywords:
EpigeneticsMicrobial genomicsMicrobial interactionsViral microbiology

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