biostudies-literatureRoodsant TJEC | Horizon 2020 Framework Programme (H2020)EC | Horizon 2020 Framework Programmee0225923https://www.ebi.ac.uk/biostudies/studies/S-EPMC10790761biostudies-literatureUnknown15(1)<h4>Importance</h4>Phase variation allows a single strain to produce phenotypic diverse subpopulations. Phase-variable restriction modification (RM) systems are systems that allow for such phase variation via epigenetic regulation of gene expression levels. The phase-variable RM system SsuCC20p was found in multiple streptococcal species and was acquired by an emerging zoonotic lineage of <i>Streptococcus suis</i>. We show that the phase variability of SsuCC20p is dependent on a recombinase encoded within the SsuCC20p locus. We characterized the genome methylation profiles of the different phases of SsuCC20p and demonstrated the consequential impact on the transcriptome and virulence in a zebrafish infection model. Acquiring mobile genetic elements containing epigenetic regulatory systems, like phase-variable RM systems, enables bacterial pathogens to produce diverse phenotypic subpopulations that are better adapted to specific (host) environments encountered during infection.mBioThe streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of <i>Streptococcus suis</i> impacting the transcriptome and virulence in a zebrafish larvae infection model.PMC10790761727966Roodsant TJSchultsz CBaltussen TJHvan der Ark KCHvan der Putten BBrizuela JCoolen JPMPannekoek YSchipper KfalseThe streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of <i>Streptococcus suis</i> impacting the transcriptome and virulence in a zebrafish larvae infection model.<h4>Importance</h4>Phase variation allows a single strain to produce phenotypic diverse subpopulations. Phase-variable restriction modification (RM) systems are systems that allow for such phase variation via epigenetic regulation of gene expression levels. The phase-variable RM system SsuCC20p was found in multiple streptococcal species and was acquired by an emerging zoonotic lineage of <i>Streptococcus suis</i>. We show that the phase variability of SsuCC20p is dependent on a recombinase encoded within the SsuCC20p locus. We characterized the genome methylation profiles of the different phases of SsuCC20p and demonstrated the consequential impact on the transcriptome and virulence in a zebrafish infection model. Acquiring mobile genetic elements containing epigenetic regulatory systems, like phase-variable RM systems, enables bacterial pathogens to produce diverse phenotypic subpopulations that are better adapted to specific (host) environments encountered during infection.2024-01-01T00:00:00Z2024 Jan2026-06-01T11:26:39.737Z2025-06-01T01:57:07.786ZS-EPMC107907613806337910.1128/mbio.02259-23