[A-OS17] Marine microbial ecology

[AOS17-03] Epigenetic interactions between bacteria and phages

★Invited Papers

*Michiko Takahashi¹ (1.National Institute of Advanced Industrial Science and Technology)

Keywords:Bacteria, Microbial ecology, Phage-host interaction, Epigenome

DNA methylation is an important epigenetic signal catalyzed by methyltransferases (MTases). In bacteria, DNA methylation-mediated biological processes affect a wide range of microbial ecologies, including phage-host interactions. There is a growing interest in epigenomic systems of diverse prokaryotes and viruses, given their importance in microbial physiology, genetics, evolution, and ecology. Restriction modification (RM) system is one of the most well-studied prokaryotic systems involved in DNA methylation that defends against foreign DNA such as conjugative plasmids and phages. Although RM systems are ubiquitous among bacteria, some phages evade RM system and adapt to their bacterial hosts. In such cases, phages are thought to stochastically acquire DNA methylation from host-encoded MTases, facilitating host adaptation. However, no study has directly compared the methylomes of hosts and phages to determine whether adapted phages acquire DNA methylation from host-encoded MTases. Here, we demonstrate the epigenetic landscape of adapted phages with diverse infection histories, focusing on the broad host-range phage KHP30T as its adapts to three Helicobacter pylori strains. Using a multistage infection system, we observed that the adapted phages showed high infectious titers against the last infected host strain but low titers against other strains, suggesting an attendant change in host tropism. Single-molecule real-time sequencing revealed that methylated motifs were predominantly shared between the adapted phages and their most recent host. Single-molecule real-time sequencing revealed that methylated motifs in the adapted phage genome were shared with those in the last-infected host strains. These findings suggest that the phage genome is modified by host-encoded MTases, resulting in the phage DNA evading cleavage by cognate REases. Our results provide direct evidence that adapted phages stochastically acquire DNA methylation from host bacteria and enhance our understanding of epigenetic phage–host interactions, which have significant implications for microbial ecology.