◆Research findings by Associate Professor Michiko Takahashi and colleagues from the Medical School of Surgery at the Medical School have been published in the academic journal *iScience*
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Elucidating the relationship between phage and bacterial infection and defense at the epigenomic level
A research group led by Medical School, Specially Appointed Assistant Medical School, and Satoshi Hiraoka, a researcher in the Marine Function Utilization Division at the Japan Agency for Marine-Earth Science and Technology (JAMSTEC), has elucidated the mechanisms by which phages that have overcome bacterial phage defense mechanisms (restriction-modification systems) alter their infectivity and DNA methylation*1 patterns.
The restriction-modification system is one of the mechanisms possessed by many bacteria to prevent the invasion of foreign DNA. Our research group generated multiple phage strains with different infection histories using phages capable of infecting Helicobacter pylori, and analyzed their infectivity*2 and epigenomes*3. The results revealed that phage strains exhibit high infectivity only against their final host and acquire different host-specificity depending on their infection history.Furthermore, it was found that the epigenomes of the phage strains generally matched those of their final hosts. This finding suggests that adaptive phages acquired DNA methylation by utilizing enzymes present in the host.
This study aims to deepen our understanding of the competition between phages and bacteria in the context of infection and defense. The findings from this study are expected to contribute to the design of phage therapy, which has recently garnered attention as an alternative treatment for antibiotic-resistant bacteria.
These research findings were published online on March 22, 2025, in the academic journal *iScience*, published by Cell Press.
*1 DNA methylation
A chemical modification in which a methyl group ( -CH₃ ) is added to the bases that make up DNA. This modification occurs after DNA replication through the action of DNA methyltransferases. It is widely observed in eukaryotes, prokaryotes, and viruses.
*2 Infectious dose
An indicator of a virus’s (phage’s) infectivity. Because viruses are so small, it is difficult to count them individually under a microscope. Therefore, the number of infectious viruses (infectivity titer) is measured by utilizing the phenomenon in which cells are destroyed by viral infection (cell lysis).
*3 Epigenome
A genome that has undergone chemical modification of its DNA. The epigenome allows genomic information to be altered without changing the nucleotide sequence. It is known to be involved in various physiological functions, such as gene expression regulation and restriction-modification systems.
[Paper Information]
Title: Host-encoded DNA methyltransferases modify the epigenome and host tropism of invading phages
DOI: 10.1016/j.isci.2025.112264
Link: https://www.cell.com/iscience/fulltext/S2589-0042(25)00525-5