{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:24:34Z","timestamp":1775197474657,"version":"3.50.1"},"reference-count":95,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Enterococcus faecalis<\/jats:italic>\n            is a commensal bacterium of the human gastrointestinal tract that causes opportunistic infections. The\n            <jats:italic>E. faecalis<\/jats:italic>\n            genetic changes associated with pathogenicity, particularly gut-to-bloodstream translocation, remain poorly understood. Here, we performed a genome-wide association study (GWAS) of 736 whole-genome sequences of fecal and bloodstream\n            <jats:italic>E. faecalis<\/jats:italic>\n            isolates from hospitalized and nonhospitalized individuals, respectively, to identify\n            <jats:italic>E. faecalis<\/jats:italic>\n            genetic signatures associated with the patient\u2019s hospitalization status and body isolation source. We found that infection by hospitalization status and extraintestinal infection are heritable traits, with ~40% and ~30% of their variation explained by\n            <jats:italic>E. faecalis<\/jats:italic>\n            genetics, respectively. Furthermore, a GWAS using linear mixed models did not pinpoint any clear overrepresentation of individual genetic changes by hospitalization status or body isolation source after controlling for the population structure. However, we observed elevated signals in a genomic region containing a prophage element. However, the lineages themselves and their associated virulence factors and antibiotic resistance genes showed variable frequency among blood and fecal isolates and in hospitalized and nonhospitalized individuals. Altogether, our findings indicate that\n            <jats:italic>E. faecalis<\/jats:italic>\n            infection by hospitalization status and body sites is partially influenced by the overall genetic background of the isolates and antibiotic resistance patterns rather than genetic variation at individual loci, which suggests a greater role of other host and environmental factors and ultimately the opportunistic pathogenic lifestyle of this versatile host generalist bacterium.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Enterococcus faecalis<\/jats:italic>\n              causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although\n              <jats:italic>E. faecalis<\/jats:italic>\n              infections cause opportunistic infections typically associated with antibiotic use, immunocompromised immune status, and other factors, they also possess an arsenal of virulence factors crucial for their pathogenicity. Despite this, the relative contribution of these virulence factors and other genetic changes to the pathogenicity of\n              <jats:italic>E. faecalis<\/jats:italic>\n              strains remain poorly understood. Here, we investigated whether specific genomic changes in the genome of\n              <jats:italic>E. faecalis<\/jats:italic>\n              isolates influence its pathogenicity\u2014infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection and intestinal colonization. Our findings indicate that\n              <jats:italic>E. faecalis<\/jats:italic>\n              genetics partially influence the infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection, possibly due to gut-to-bloodstream translocation, highlighting the potential substantial role of host and environmental factors, including gut microbiota, on the opportunistic pathogenic lifestyle of this bacterium.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00201-23","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T13:01:54Z","timestamp":1696856514000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["The population-level impact of\n            <i>Enterococcus faecalis<\/i>\n            genetics on intestinal colonization and extraintestinal infection"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-1757","authenticated-orcid":true,"given":"Chrispin","family":"Chaguza","sequence":"first","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University , New Haven, Connecticut, USA"},{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus , Cambridge, United Kingdom"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-2042","authenticated-orcid":false,"given":"Anna K.","family":"P\u00f6ntinen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, University of Oslo , Oslo, Norway"},{"name":"Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway , Troms\u00f8, Norway"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4620-8128","authenticated-orcid":true,"given":"Janetta","family":"Top","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Medical Center Utrecht , Utrecht, the Netherlands"}]},{"given":"Sergio","family":"Arredondo-Alonso","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus , Cambridge, United Kingdom"},{"name":"Department of Biostatistics, Faculty of Medicine, University of Oslo , Oslo, Norway"}]},{"given":"Ana R.","family":"Freitas","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Microbiology, Department of Biological Sciences, REQUIMTE Faculty of Pharmacy, University of Porto , Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto , Porto, Portugal"},{"name":"TOXRUN, Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL , Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-6731","authenticated-orcid":true,"given":"Carla","family":"Novais","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Microbiology, Department of Biological Sciences, REQUIMTE Faculty of Pharmacy, University of Porto , Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto , Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-1690","authenticated-orcid":true,"given":"Carmen","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Food and Agriculture, Area of Biochemistry and Molecular Biology, University of La Rioja , Logro\u00f1o, Spain"}]},{"given":"Stephen D.","family":"Bentley","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus , Cambridge, United Kingdom"}]},{"given":"Luisa","family":"Peixe","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Microbiology, Department of Biological Sciences, REQUIMTE Faculty of Pharmacy, University of Porto , Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto , Porto, Portugal"}]},{"given":"Teresa M.","family":"Coque","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Ram\u00f3n y Cajal University Hospital, Ram\u00f3n y Cajal Institute for Health Research (IRYCIS) , Madrid, Spain"},{"name":"CIBER in Infectious Diseases (CIBERINFEC) , Madrid, Spain"}]},{"given":"Rob J. 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