Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification

ABSTRACT Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seve...

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Autores principales:	Jean Y. H. Lee, Glen P. Carter, Sacha J. Pidot, Romain Guérillot, Torsten Seemann, Anders Gonçalves da Silva, Timothy J. Foster, Benjamin P. Howden, Timothy P. Stinear, Ian R. Monk
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	DNA methylation Staphylococcus aureus coagulase-negative staphylococci generalized transduction genetic manipulation genome analysis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e3d32570b9ae423490b78ed214e1e8af
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spelling	oai:doaj.org-article:e3d32570b9ae423490b78ed214e1e8af2021-11-15T15:54:46ZMining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification10.1128/mBio.02451-192150-7511https://doaj.org/article/e3d32570b9ae423490b78ed214e1e8af2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02451-19https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse S. epidermidis isolates and perform the first systematic genomic analyses of the type I RM systems within both S. epidermidis and Staphylococcus aureus. Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species. Unlike S. aureus, S. epidermidis type I RM systems demonstrate extensive diversity even within a single genetic lineage. This is contrary to current assumptions and has important implications for approaching the genetic manipulation of S. epidermidis. Using Escherichia coli plasmid artificial modification (PAM) to express S. epidermidis hsdMS, we readily overcame restriction barriers in S. epidermidis and achieved electroporation efficiencies equivalent to those of modification-deficient mutants. With these functional experiments, we demonstrated how genomic data can be used to predict both the functionality of type I RM systems and the potential for a strain to be electroporation proficient. We outline an efficient approach for the genetic manipulation of S. epidermidis strains from diverse genetic backgrounds, including those that have hitherto been intractable. Additionally, we identified S. epidermidis BPH0736, a naturally restriction-defective, clinically significant, multidrug-resistant ST2 isolate, as an ideal candidate for molecular studies. IMPORTANCE Staphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections have been hindered by an inability to genetically manipulate clinically significant hospital-adapted strains. Here, we provide the first comprehensive analyses of the barriers to the uptake of foreign DNA in S. epidermidis and demonstrate that these are distinct from those described for S. aureus. Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinical isolates for the first time.Jean Y. H. LeeGlen P. CarterSacha J. PidotRomain GuérillotTorsten SeemannAnders Gonçalves da SilvaTimothy J. FosterBenjamin P. HowdenTimothy P. StinearIan R. MonkAmerican Society for MicrobiologyarticleDNA methylationStaphylococcus aureuscoagulase-negative staphylococcigeneralized transductiongenetic manipulationgenome analysisMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA methylation Staphylococcus aureus coagulase-negative staphylococci generalized transduction genetic manipulation genome analysis Microbiology QR1-502
spellingShingle	DNA methylation Staphylococcus aureus coagulase-negative staphylococci generalized transduction genetic manipulation genome analysis Microbiology QR1-502 Jean Y. H. Lee Glen P. Carter Sacha J. Pidot Romain Guérillot Torsten Seemann Anders Gonçalves da Silva Timothy J. Foster Benjamin P. Howden Timothy P. Stinear Ian R. Monk Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
description	ABSTRACT Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse S. epidermidis isolates and perform the first systematic genomic analyses of the type I RM systems within both S. epidermidis and Staphylococcus aureus. Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species. Unlike S. aureus, S. epidermidis type I RM systems demonstrate extensive diversity even within a single genetic lineage. This is contrary to current assumptions and has important implications for approaching the genetic manipulation of S. epidermidis. Using Escherichia coli plasmid artificial modification (PAM) to express S. epidermidis hsdMS, we readily overcame restriction barriers in S. epidermidis and achieved electroporation efficiencies equivalent to those of modification-deficient mutants. With these functional experiments, we demonstrated how genomic data can be used to predict both the functionality of type I RM systems and the potential for a strain to be electroporation proficient. We outline an efficient approach for the genetic manipulation of S. epidermidis strains from diverse genetic backgrounds, including those that have hitherto been intractable. Additionally, we identified S. epidermidis BPH0736, a naturally restriction-defective, clinically significant, multidrug-resistant ST2 isolate, as an ideal candidate for molecular studies. IMPORTANCE Staphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections have been hindered by an inability to genetically manipulate clinically significant hospital-adapted strains. Here, we provide the first comprehensive analyses of the barriers to the uptake of foreign DNA in S. epidermidis and demonstrate that these are distinct from those described for S. aureus. Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinical isolates for the first time.
format	article
author	Jean Y. H. Lee Glen P. Carter Sacha J. Pidot Romain Guérillot Torsten Seemann Anders Gonçalves da Silva Timothy J. Foster Benjamin P. Howden Timothy P. Stinear Ian R. Monk
author_facet	Jean Y. H. Lee Glen P. Carter Sacha J. Pidot Romain Guérillot Torsten Seemann Anders Gonçalves da Silva Timothy J. Foster Benjamin P. Howden Timothy P. Stinear Ian R. Monk
author_sort	Jean Y. H. Lee
title	Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
title_short	Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
title_full	Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
title_fullStr	Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
title_full_unstemmed	Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification
title_sort	mining the methylome reveals extensive diversity in <named-content content-type="genus-species">staphylococcus epidermidis</named-content> restriction modification
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e3d32570b9ae423490b78ed214e1e8af
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Mining the Methylome Reveals Extensive Diversity in <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> Restriction Modification

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