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Dam-dependent epigenetic memory regulates prophage reintegration in Salmonella
Jihye Yang1, Yongjun Son1, Jinwon Park1
1Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul 02841, Republic of Korea.
Nucleic Acids Research
|September 23, 2025
Summary
Salmonella enterica uses epigenetic memory to reintegrate prophage DNA after stress. DNA adenine methyltransferase (Dam) activity and promoter methylation maintain gene expression for successful phage reintegration during infection.
Area of Science:
- Microbiology
- Epigenetics
- Bacterial Pathogenesis
Background:
- Bacterial epigenetics regulates gene expression in response to environmental changes.
- The persistence of epigenetic modifications after stress removal is not well understood.
- Prophage dynamics are crucial for bacterial adaptation and evolution.
Purpose of the Study:
- To investigate the role of epigenetic modifications in Salmonella enterica during infection.
- To determine if epigenetic changes persist after stress and influence prophage behavior.
- To elucidate the mechanism of prophage reintegration and its epigenetic regulation.
Main Methods:
- In vitro model of Salmonella infection cycle, including the Salmonella-containing vacuole (SCV).
- Analysis of DNA adenine methyltransferase (Dam) activity and global methylation patterns.
- Functional assays to assess prophage ST64B excision and reintegration.
- Investigation of intA promoter methylation and its effect on transcription.
Main Results:
- Oxidative stress during early SCV stages induces prophage ST64B excision.
- Increased global methylation, particularly at the intA promoter, occurs at later infection stages.
- This methylation persists after stress removal, maintaining active intA transcription and establishing epigenetic memory.
- intA expression, dependent on promoter methylation, is essential for efficient ST64B reintegration.
Conclusions:
- Salmonella possesses an epigenetic memory system involving Dam-mediated methylation of the intA promoter.
- This system facilitates prophage ST64B reintegration by sustaining intA expression after stress.
- Stress-responsive epigenetic control is vital for Salmonella adaptation and pathogenesis.
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