Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium

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Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium. / Arredondo-Alonso, Sergio; Top, Janetta; McNally, Alan; Puranen, Santeri; Pesonen, Maiju; Pensar, Johan; Marttinen, Pekka; Braat, Johanna; Rogers, Malbert; van Schaik, Willem; Kaski, Samuel; Willems, Rob J L; Corander, Jukka; Schürch, Anita.

In: MBIO, Vol. 11, No. 1, e03284-19, 2020.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Arredondo-Alonso, S, Top, J, McNally, A, Puranen, S, Pesonen, M, Pensar, J, Marttinen, P, Braat, J, Rogers, M, van Schaik, W, Kaski, S, Willems, RJL, Corander, J & Schürch, A 2020, 'Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium', MBIO, vol. 11, no. 1, e03284-19. https://doi.org/10.1128/mBio.03284-19

APA

Arredondo-Alonso, S., Top, J., McNally, A., Puranen, S., Pesonen, M., Pensar, J., ... Schürch, A. (2020). Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium. MBIO, 11(1), [e03284-19]. https://doi.org/10.1128/mBio.03284-19

Vancouver

Author

Arredondo-Alonso, Sergio ; Top, Janetta ; McNally, Alan ; Puranen, Santeri ; Pesonen, Maiju ; Pensar, Johan ; Marttinen, Pekka ; Braat, Johanna ; Rogers, Malbert ; van Schaik, Willem ; Kaski, Samuel ; Willems, Rob J L ; Corander, Jukka ; Schürch, Anita. / Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium. In: MBIO. 2020 ; Vol. 11, No. 1.

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@article{31f170c602bf4d8c821b9f0c186c8ad5,
title = "Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium",
abstract = "Enterococcus faecium is a gut commensal of humans and animals but is also listed on the WHO global priority list of multidrug-resistant pathogens. Many of its antibiotic resistance traits reside on plasmids and have the potential to be disseminated by horizontal gene transfer. Here, we present the first comprehensive population-wide analysis of the pan-plasmidome of a clinically important bacterium, by whole-genome sequence analysis of 1,644 isolates from hospital, commensal, and animal sources of E. faecium. Long-read sequencing on a selection of isolates resulted in the completion of 305 plasmids that exhibited high levels of sequence modularity. We further investigated the entirety of all plasmids of each isolate (plas-midome) using a combination of short-read sequencing and machine-learning classi-fiers. Clustering of the plasmid sequences unraveled different E. faecium populations with a clear association with hospitalized patient isolates, suggesting different optimal configurations of plasmids in the hospital environment. The characterization of these populations allowed us to identify common mechanisms of plasmid stabilization such as toxin-antitoxin systems and genes exclusively present in particular plasmidome populations exemplified by copper resistance, phosphotransferase systems, or bacteriocin genes potentially involved in niche adaptation. Based on the distribution of k-mer distances between isolates, we concluded that plasmidomes rather than chromosomes are most informative for source specificity of E. faecium. IMPORTANCE Enterococcus faecium is one of the most frequent nosocomial pathogens of hospital-acquired infections. E. faecium has gained resistance against most commonly available antibiotics, most notably, against ampicillin, gentamicin, and vancomycin, which renders infections difficult to treat. Many antibiotic resistance traits, in particular, vancomycin resistance, can be encoded in autonomous and extrachromosomal elements called plasmids. These sequences can be disseminated to other isolates by horizontal gene transfer and confer novel mechanisms to source specificity. In our study, we elucidated the total plasmid content, referred to as the plasmidome, of 1,644 E. faecium isolates by using short-and long-read whole-genome technologies with the combination of a machine-learning classifier. This was fundamental to investigate the full collection of plasmid sequences present in our collection (pan-plasmidome) and to observe the potential transfer of plasmid sequences between E. faecium hosts. We observed that E. faecium isolates from hospitalized patients carried a larger number of plasmid sequences compared to that from other sources, and they elucidated different configurations of plasmidome populations in the hospital environment. We assessed the contribution of different genomic components and observed that plasmid sequences have the highest contribution to source specificity. Our study suggests that E. faecium plasmids are regulated by complex ecological constraints rather than physical interaction between hosts.",
keywords = "Enterococcus faecium, Long-read sequencing, Machine learning, Nosocomial pathogen, Plasmidome, Source specificity",
author = "Sergio Arredondo-Alonso and Janetta Top and Alan McNally and Santeri Puranen and Maiju Pesonen and Johan Pensar and Pekka Marttinen and Johanna Braat and Malbert Rogers and {van Schaik}, Willem and Samuel Kaski and Willems, {Rob J L} and Jukka Corander and Anita Sch{\"u}rch",
note = "| openaire: EC/H2020/742158/EU//SCARABEE",
year = "2020",
doi = "10.1128/mBio.03284-19",
language = "English",
volume = "11",
journal = "MBIO",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "1",

}

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TY - JOUR

T1 - Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium

AU - Arredondo-Alonso, Sergio

AU - Top, Janetta

AU - McNally, Alan

AU - Puranen, Santeri

AU - Pesonen, Maiju

AU - Pensar, Johan

AU - Marttinen, Pekka

AU - Braat, Johanna

AU - Rogers, Malbert

AU - van Schaik, Willem

AU - Kaski, Samuel

AU - Willems, Rob J L

AU - Corander, Jukka

AU - Schürch, Anita

N1 - | openaire: EC/H2020/742158/EU//SCARABEE

PY - 2020

Y1 - 2020

N2 - Enterococcus faecium is a gut commensal of humans and animals but is also listed on the WHO global priority list of multidrug-resistant pathogens. Many of its antibiotic resistance traits reside on plasmids and have the potential to be disseminated by horizontal gene transfer. Here, we present the first comprehensive population-wide analysis of the pan-plasmidome of a clinically important bacterium, by whole-genome sequence analysis of 1,644 isolates from hospital, commensal, and animal sources of E. faecium. Long-read sequencing on a selection of isolates resulted in the completion of 305 plasmids that exhibited high levels of sequence modularity. We further investigated the entirety of all plasmids of each isolate (plas-midome) using a combination of short-read sequencing and machine-learning classi-fiers. Clustering of the plasmid sequences unraveled different E. faecium populations with a clear association with hospitalized patient isolates, suggesting different optimal configurations of plasmids in the hospital environment. The characterization of these populations allowed us to identify common mechanisms of plasmid stabilization such as toxin-antitoxin systems and genes exclusively present in particular plasmidome populations exemplified by copper resistance, phosphotransferase systems, or bacteriocin genes potentially involved in niche adaptation. Based on the distribution of k-mer distances between isolates, we concluded that plasmidomes rather than chromosomes are most informative for source specificity of E. faecium. IMPORTANCE Enterococcus faecium is one of the most frequent nosocomial pathogens of hospital-acquired infections. E. faecium has gained resistance against most commonly available antibiotics, most notably, against ampicillin, gentamicin, and vancomycin, which renders infections difficult to treat. Many antibiotic resistance traits, in particular, vancomycin resistance, can be encoded in autonomous and extrachromosomal elements called plasmids. These sequences can be disseminated to other isolates by horizontal gene transfer and confer novel mechanisms to source specificity. In our study, we elucidated the total plasmid content, referred to as the plasmidome, of 1,644 E. faecium isolates by using short-and long-read whole-genome technologies with the combination of a machine-learning classifier. This was fundamental to investigate the full collection of plasmid sequences present in our collection (pan-plasmidome) and to observe the potential transfer of plasmid sequences between E. faecium hosts. We observed that E. faecium isolates from hospitalized patients carried a larger number of plasmid sequences compared to that from other sources, and they elucidated different configurations of plasmidome populations in the hospital environment. We assessed the contribution of different genomic components and observed that plasmid sequences have the highest contribution to source specificity. Our study suggests that E. faecium plasmids are regulated by complex ecological constraints rather than physical interaction between hosts.

AB - Enterococcus faecium is a gut commensal of humans and animals but is also listed on the WHO global priority list of multidrug-resistant pathogens. Many of its antibiotic resistance traits reside on plasmids and have the potential to be disseminated by horizontal gene transfer. Here, we present the first comprehensive population-wide analysis of the pan-plasmidome of a clinically important bacterium, by whole-genome sequence analysis of 1,644 isolates from hospital, commensal, and animal sources of E. faecium. Long-read sequencing on a selection of isolates resulted in the completion of 305 plasmids that exhibited high levels of sequence modularity. We further investigated the entirety of all plasmids of each isolate (plas-midome) using a combination of short-read sequencing and machine-learning classi-fiers. Clustering of the plasmid sequences unraveled different E. faecium populations with a clear association with hospitalized patient isolates, suggesting different optimal configurations of plasmids in the hospital environment. The characterization of these populations allowed us to identify common mechanisms of plasmid stabilization such as toxin-antitoxin systems and genes exclusively present in particular plasmidome populations exemplified by copper resistance, phosphotransferase systems, or bacteriocin genes potentially involved in niche adaptation. Based on the distribution of k-mer distances between isolates, we concluded that plasmidomes rather than chromosomes are most informative for source specificity of E. faecium. IMPORTANCE Enterococcus faecium is one of the most frequent nosocomial pathogens of hospital-acquired infections. E. faecium has gained resistance against most commonly available antibiotics, most notably, against ampicillin, gentamicin, and vancomycin, which renders infections difficult to treat. Many antibiotic resistance traits, in particular, vancomycin resistance, can be encoded in autonomous and extrachromosomal elements called plasmids. These sequences can be disseminated to other isolates by horizontal gene transfer and confer novel mechanisms to source specificity. In our study, we elucidated the total plasmid content, referred to as the plasmidome, of 1,644 E. faecium isolates by using short-and long-read whole-genome technologies with the combination of a machine-learning classifier. This was fundamental to investigate the full collection of plasmid sequences present in our collection (pan-plasmidome) and to observe the potential transfer of plasmid sequences between E. faecium hosts. We observed that E. faecium isolates from hospitalized patients carried a larger number of plasmid sequences compared to that from other sources, and they elucidated different configurations of plasmidome populations in the hospital environment. We assessed the contribution of different genomic components and observed that plasmid sequences have the highest contribution to source specificity. Our study suggests that E. faecium plasmids are regulated by complex ecological constraints rather than physical interaction between hosts.

KW - Enterococcus faecium

KW - Long-read sequencing

KW - Machine learning

KW - Nosocomial pathogen

KW - Plasmidome

KW - Source specificity

U2 - 10.1128/mBio.03284-19

DO - 10.1128/mBio.03284-19

M3 - Article

C2 - 32047136

VL - 11

JO - MBIO

JF - MBIO

SN - 2161-2129

IS - 1

M1 - e03284-19

ER -

ID: 40342057