A Type I Restriction-Modification System Associated with Enterococcus Faecium Subspecies Separation

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dc.contributor.ORCID0000-0002-7343-9271 (Palmer, KL)
dc.contributor.authorHuo, Wenwen
dc.contributor.authorAdams, Hannah M.
dc.contributor.authorTrejo, Cristian
dc.contributor.authorBadia, Rohit
dc.contributor.authorPalmer, Kelli L.
dc.contributor.utdAuthorHuo, Wenwen
dc.contributor.utdAuthorAdams, Hannah M.
dc.contributor.utdAuthorTrejo, Cristian
dc.contributor.utdAuthorBadia, Rohit
dc.contributor.utdAuthorPalmer, Kelli L.
dc.date.accessioned2020-05-07T16:26:50Z
dc.date.available2020-05-07T16:26:50Z
dc.date.issued2019-01-09
dc.description.abstractThe gastrointestinal colonizer Enterococcus faecium is a leading cause of hospital-acquired infections. Multidrug-resistant (MDR) E. faecium isolates are particularly concerning for infection treatment. Previous comparative genomic studies revealed that subspecies referred to as clade A and clade B exist within E. faecium. MDR E. faecium isolates belong to clade A, while clade B consists of drug-susceptible fecal commensal E. faecium isolates. Isolates from clade A are further grouped into two subclades, clades A1 and A2. In general, clade A1 isolates are hospital-epidemic isolates, whereas clade A2 isolates are isolates from animals and sporadic human infections. Such phylogenetic separation indicates that reduced gene exchange occurs between the clades. We hypothesize that endogenous barriers to gene exchange exist between E. faecium clades. Restriction-modification (R-M) systems are such barriers in other microbes. We utilized a bioinformatics analysis coupled with second-generation and third-generation deep-sequencing platforms to characterize the methylomes of two representative E. faecium strains, one from clade A1 and one from clade B. We identified a type I R-M system that is clade A1 specific, is active for DNA methylation, and significantly reduces the transformability of clade A1 E. faecium. Based on our results, we conclude that R-M systems act as barriers to horizontal gene exchange in E. faecium and propose that R-M systems contribute to E. faecium subspecies separation. IMPORTANCE Enterococcus faecium is a leading cause of hospital-acquired infections around the world. Rising antibiotic resistance in certain E. faecium lineages leaves fewer treatment options. The overarching aim of this work was to determine whether restriction-modification (R-M) systems contribute to the structure of the E. faecium species, wherein hospital-epidemic and non-hospital-epidemic isolates have distinct evolutionary histories and highly resolved clade structures. R-M provides bacteria with a type of innate immunity to horizontal gene transfer (HGT). We identified a type I R-M system that is enriched in the hospital-epidemic clade and determined that it is active for DNA modification activity and significantly impacts HGT. Overall, this work is important because it provides a mechanism for the observed clade structure of E. faecium as well as a mechanism for facilitated gene exchange among hospital-epidemic E. faecium isolates.
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.sponsorshipPublic Health Service grants K22AI099088 and R01AI116610
dc.identifier.bibliographicCitationHuo, Wenwen, Hannah M. Adams, Cristian Trejo, Rohit Badia, et al. 2019. "A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation." Applied and Environmental Microbiology 85(2): art. e02174-18, doi: 10.1128/AEM.02174-18
dc.identifier.issn0099-2240
dc.identifier.issue2
dc.identifier.urihttp://dx.doi.org/10.1128/AEM.02174-18
dc.identifier.urihttps://hdl.handle.net/10735.1/8532
dc.identifier.volume85
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.rightsCC BY 4.0 (Attribution)
dc.rights©2019 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.journalApplied and Environmental Microbiology
dc.subjectGenomes
dc.subjectEnzymes
dc.subjectGenes
dc.subject.meshDNA Restriction-Modification Enzymes
dc.subject.meshEnterococcus faecium
dc.subject.meshDrug Resistance, Microbial
dc.subject.meshEscherichia coli
dc.subject.meshDNA Methylation
dc.titleA Type I Restriction-Modification System Associated with Enterococcus Faecium Subspecies Separation
dc.type.genrearticle

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Palmer, Kelli L.