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

The 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...

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Autores principales: Huo, Wenwen, Adams, Hannah M., Trejo, Cristian, Badia, Rohit, Palmer, Kelli L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328761/
https://www.ncbi.nlm.nih.gov/pubmed/30389763
http://dx.doi.org/10.1128/AEM.02174-18
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author Huo, Wenwen
Adams, Hannah M.
Trejo, Cristian
Badia, Rohit
Palmer, Kelli L.
author_facet Huo, Wenwen
Adams, Hannah M.
Trejo, Cristian
Badia, Rohit
Palmer, Kelli L.
author_sort Huo, Wenwen
collection PubMed
description The 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.
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spelling pubmed-63287612019-02-01 A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation Huo, Wenwen Adams, Hannah M. Trejo, Cristian Badia, Rohit Palmer, Kelli L. Appl Environ Microbiol Evolutionary and Genomic Microbiology The 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. American Society for Microbiology 2019-01-09 /pmc/articles/PMC6328761/ /pubmed/30389763 http://dx.doi.org/10.1128/AEM.02174-18 Text en Copyright © 2019 Huo et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Evolutionary and Genomic Microbiology
Huo, Wenwen
Adams, Hannah M.
Trejo, Cristian
Badia, Rohit
Palmer, Kelli L.
A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title_full A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title_fullStr A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title_full_unstemmed A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title_short A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation
title_sort type i restriction-modification system associated with enterococcus faecium subspecies separation
topic Evolutionary and Genomic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328761/
https://www.ncbi.nlm.nih.gov/pubmed/30389763
http://dx.doi.org/10.1128/AEM.02174-18
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