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

dc.contributorAalto Universityen
dc.contributor.authorArredondo-Alonso, Sergioen_US
dc.contributor.authorTop, Janettaen_US
dc.contributor.authorMcNally, Alanen_US
dc.contributor.authorPuranen, Santerien_US
dc.contributor.authorPesonen, Maijuen_US
dc.contributor.authorPensar, Johanen_US
dc.contributor.authorMarttinen, Pekkaen_US
dc.contributor.authorBraat, Johannaen_US
dc.contributor.authorRogers, Malberten_US
dc.contributor.authorvan Schaik, Willemen_US
dc.contributor.authorKaski, Samuelen_US
dc.contributor.authorWillems, Rob J Len_US
dc.contributor.authorCorander, Jukkaen_US
dc.contributor.authorSchürch, Anitaen_US
dc.contributor.departmentDepartment of Computer Scienceen
dc.contributor.groupauthorProfessorship Kaski Samuelen
dc.contributor.groupauthorHelsinki Institute for Information Technology (HIIT)en
dc.contributor.groupauthorCentre of Excellence in Computational Inference, COINen
dc.contributor.groupauthorFinnish Center for Artificial Intelligence, FCAIen
dc.contributor.groupauthorProbabilistic Machine Learningen
dc.contributor.organizationUtrecht Universityen_US
dc.contributor.organizationUniversity of Birminghamen_US
dc.contributor.organizationUniversity of Helsinkien_US
dc.description| openaire: EC/H2020/742158/EU//SCARABEE
dc.description.abstractEnterococcus 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.en
dc.description.versionPeer revieweden
dc.identifier.citationArredondo-Alonso, S, Top, J, McNally, A, Puranen, S, Pesonen, M, Pensar, J, Marttinen, P, Braat, J, Rogers, M, van Schaik, W, Kaski, S, Willems, R J L, Corander, J & Schürch, A 2020, ' Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium ', MBIO, vol. 11, no. 1, e03284-19 .
dc.identifier.otherPURE UUID: 31f170c6-02bf-4d8c-821b-9f0c186c8ad5en_US
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dc.publisherAmerican Society for Microbiology
dc.relation.ispartofseriesVolume 11, issue 1en
dc.subject.keywordEnterococcus faeciumen_US
dc.subject.keywordLong-read sequencingen_US
dc.subject.keywordMachine learningen_US
dc.subject.keywordNosocomial pathogenen_US
dc.subject.keywordSource specificityen_US
dc.titlePlasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faeciumen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi