{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:47:21Z","timestamp":1792262841399,"version":"4.4.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI083214"],"award-info":[{"award-number":["AI083214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI124302"],"award-info":[{"award-number":["AI124302"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI110618"],"award-info":[{"award-number":["AI110618"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["EY028222"],"award-info":[{"award-number":["EY028222"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:p>\n                    Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistant\n                    <jats:italic>Enterococcus faecium<\/jats:italic>\n                    (VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal and blood cultures of 24 pediatric patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancy at St. Jude Children\u2019s Research Hospital. We used patient-specific reference genomes to identify variants that arose over time in subsequent gastrointestinal and blood isolates from each patient and analyzed these variants for insight into how VREfm adapted during colonization and bloodstream infection within each patient. Variants were enriched in genes involved in carbohydrate metabolism, and phenotypic analysis identified associated differences in carbohydrate utilization among isolates. In particular, a Y585C mutation in the sorbitol operon transcriptional regulator\n                    <jats:italic>gutR<\/jats:italic>\n                    was associated with increased bacterial growth in the presence of sorbitol. We also found differences in biofilm-formation capability between isolates and observed that increased biofilm formation correlated with mutations in the putative\n                    <jats:italic>E. faecium<\/jats:italic>\n                    capsular polysaccharide (\n                    <jats:italic>cps<\/jats:italic>\n                    ) biosynthetic locus, with different mutations arising independently in distinct genetic backgrounds. Isolates with\n                    <jats:italic>cps<\/jats:italic>\n                    mutations showed improved survival following exposure to lysozyme, suggesting a possible reason for the selection of capsule-lacking bacteria. Finally, we observed mutations conferring increased tolerance of linezolid and daptomycin in patients who were treated with these antibiotics. Overall, this study documents known and previously undescribed ways that VREfm evolve during intestinal colonization and subsequent bloodstream infection in immunocompromised pediatric patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1917130117","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T20:26:04Z","timestamp":1589228764000},"page":"11703-11714","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Evolution of vancomycin-resistant\n                    <i>Enterococcus faecium<\/i>\n                    during colonization and infection in immunocompromised pediatric patients"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5247-5399","authenticated-orcid":false,"given":"Gayatri Shankar","family":"Chilambi","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley R.","family":"Nordstrom","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-5507","authenticated-orcid":false,"given":"Jose A.","family":"Ferrolino","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall T.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M.","family":"Mar\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"},{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh N.","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"},{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA 02114;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"},{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1798-1760","authenticated-orcid":false,"given":"Jason W.","family":"Rosch","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-0103","authenticated-orcid":false,"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-micro-091213-113003","article-title":"Friend turned foe: Evolution of enterococcal virulence and antibiotic resistance","volume":"68","author":"Van Tyne D.","year":"2014","unstructured":"D. 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