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Prevalence of phase variable epigenetic invertons among host-associated bacteria
Xueting Huang1,2, Juanjuan Wang1, Jing Li1
1Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing 100084, China.
Invertase enzymes drive DNA inversions in bacterial epigenetic invertons, altering gene expression and impacting host adaptation. This epigenetic switching mechanism is widespread in host-associated bacteria.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Type I restriction-modification (R-M) systems utilize DNA endonuclease and methyltransferase subunits.
- Specific hsdS sequences within R-M systems, termed epigenetic invertons, can undergo DNA inversions catalyzed by invertase enzymes.
- Previous research in *Streptococcus pneumoniae* demonstrated that hsdS inversions lead to significant variations in methylome, physiology, and virulence within bacterial populations.
Purpose of the Study:
- To bioinformatically identify and characterize invertase homologs involved in hsdS inversions across diverse bacterial phyla.
- To investigate the prevalence and function of epigenetic invertons in host-associated bacteria.
- To elucidate the impact of hsdS allelic variations on gene expression and bacterial adaptation.
Main Methods:
- Bioinformatic analysis to identify invertase homologs and their distribution.
- Experimental verification of hsdS inversions in Type I R-M systems of host-associated bacteria.
- Transcriptome analysis to assess gene expression changes due to hsdS allelic variations.
Main Results:
- Six major clades of tyrosine and serine family invertase homologs were identified, suggesting broad potential for hsdS inversions.
- Epigenetic invertons are significantly enriched in bacteria associated with hosts.
- Verified hsdS inversions in four host-associated bacteria, with each allelic variant controlling unique DNA methylation.
- Transcriptome analysis in *Enterococcus faecalis* revealed that hsdS variations substantially affect gene expression.
Conclusions:
- Invertase-driven epigenetic switches within epigenetic invertons are prevalent in host-associated bacteria.
- These epigenetic mechanisms contribute to bacterial host adaptation and virulence, extending beyond their role in R-M systems against phages.
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