The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model
ABSTRACTPhase-variable type I restriction modification (RM) systems are epigenetic regulatory systems that have been identified in numerous human bacterial pathogens. We previously showed that an emerging zoonotic lineage of Streptococcus suis acquired a phase-variable type I RM system, named SsuCC2...
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| Language: | English |
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American Society for Microbiology
2024-01-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02259-23 |
| _version_ | 1797353854232166400 |
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| author | Thomas J. Roodsant Boas van der Putten Jaime Brizuela Jordy P. M. Coolen Tim J. H. Baltussen Kim Schipper Yvonne Pannekoek Kees C. H. van der Ark Constance Schultsz |
| author_facet | Thomas J. Roodsant Boas van der Putten Jaime Brizuela Jordy P. M. Coolen Tim J. H. Baltussen Kim Schipper Yvonne Pannekoek Kees C. H. van der Ark Constance Schultsz |
| author_sort | Thomas J. Roodsant |
| collection | DOAJ |
| description | ABSTRACTPhase-variable type I restriction modification (RM) systems are epigenetic regulatory systems that have been identified in numerous human bacterial pathogens. We previously showed that an emerging zoonotic lineage of Streptococcus suis acquired a phase-variable type I RM system, named SsuCC20p. The SsuCC20p locus was identified in the genome of multiple streptococcal species, indicating that it is not restricted to S. suis and can be acquired through horizontal gene transfer. We demonstrate that SsuCC20p phase variability relies on a recombinase present within the locus. SsuCC20p is the single RM system responsible for the genome methylation profiles that were detected in the representative zoonotic S. suis isolate 861160 in vitro. In addition, we show that, contrary to previous observations, hsdS genes located downstream of hsdM and the recombinase gene contribute to the SsuCC20p genome methylation profile. SsuCC20p locked mutants expressing a single hsdS each show a unique genome methylation profile and, when grown in human serum, have distinct transcriptomes. In a zebrafish larvae infection model, we observed significant differences in virulence between the locked mutants and a corresponding shift in hsdS allele distribution in the wild type. These data indicate that the streptococcal phase-variable type I RM system SsuCC20p can impact bacterial fitness via epigenetic regulation of gene expression, which impacts the virulence of S. suis in the zebrafish larvae infection model.IMPORTANCEPhase 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 Streptococcus suis. 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. |
| first_indexed | 2024-03-08T13:36:59Z |
| format | Article |
| id | doaj.art-139c363bb5a14f29b9d0177836416bdf |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-03-08T13:36:59Z |
| publishDate | 2024-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-139c363bb5a14f29b9d0177836416bdf2024-01-16T15:40:00ZengAmerican Society for MicrobiologymBio2150-75112024-01-0115110.1128/mbio.02259-23The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection modelThomas J. Roodsant0Boas van der Putten1Jaime Brizuela2Jordy P. M. Coolen3Tim J. H. Baltussen4Kim Schipper5Yvonne Pannekoek6Kees C. H. van der Ark7Constance Schultsz8Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the NetherlandsDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the NetherlandsABSTRACTPhase-variable type I restriction modification (RM) systems are epigenetic regulatory systems that have been identified in numerous human bacterial pathogens. We previously showed that an emerging zoonotic lineage of Streptococcus suis acquired a phase-variable type I RM system, named SsuCC20p. The SsuCC20p locus was identified in the genome of multiple streptococcal species, indicating that it is not restricted to S. suis and can be acquired through horizontal gene transfer. We demonstrate that SsuCC20p phase variability relies on a recombinase present within the locus. SsuCC20p is the single RM system responsible for the genome methylation profiles that were detected in the representative zoonotic S. suis isolate 861160 in vitro. In addition, we show that, contrary to previous observations, hsdS genes located downstream of hsdM and the recombinase gene contribute to the SsuCC20p genome methylation profile. SsuCC20p locked mutants expressing a single hsdS each show a unique genome methylation profile and, when grown in human serum, have distinct transcriptomes. In a zebrafish larvae infection model, we observed significant differences in virulence between the locked mutants and a corresponding shift in hsdS allele distribution in the wild type. These data indicate that the streptococcal phase-variable type I RM system SsuCC20p can impact bacterial fitness via epigenetic regulation of gene expression, which impacts the virulence of S. suis in the zebrafish larvae infection model.IMPORTANCEPhase 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 Streptococcus suis. 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.https://journals.asm.org/doi/10.1128/mbio.02259-23Streptococcus suiszoonosistype I restriction modification systemphase-variationDNA methylationepigenetic regulation |
| spellingShingle | Thomas J. Roodsant Boas van der Putten Jaime Brizuela Jordy P. M. Coolen Tim J. H. Baltussen Kim Schipper Yvonne Pannekoek Kees C. H. van der Ark Constance Schultsz The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model mBio Streptococcus suis zoonosis type I restriction modification system phase-variation DNA methylation epigenetic regulation |
| title | The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| title_full | The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| title_fullStr | The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| title_full_unstemmed | The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| title_short | The streptococcal phase-variable type I restriction modification system SsuCC20p dictates the methylome of Streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| title_sort | streptococcal phase variable type i restriction modification system ssucc20p dictates the methylome of streptococcus suis impacting the transcriptome and virulence in a zebrafish larvae infection model |
| topic | Streptococcus suis zoonosis type I restriction modification system phase-variation DNA methylation epigenetic regulation |
| url | https://journals.asm.org/doi/10.1128/mbio.02259-23 |
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