{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:09:14Z","timestamp":1789664954909,"version":"4.0.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:00:00Z","timestamp":1608940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Norwegian National Advisory Unit on Detection of Antimicrobial Resistance"},{"name":"Department of Microbiology and Infection Control"},{"name":"National Graduate School in Infection Biology and Antimicrobials","award":["249062"],"award-info":[{"award-number":["249062"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Vancomycin variable enterococci (VVE) are van-positive isolates with a susceptible phenotype that can convert to a resistant phenotype during vancomycin selection.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To describe a vancomycin-susceptible vanA-PCR positive ST203 VVE Enterococcus faecium isolate (VVESwe-S) from a liver transplantation patient in Sweden which reverted to resistant (VVESwe-R) during in vitro vancomycin exposure.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n WGS analysis revealed the genetic differences between the isolates. Expression of the van-operon was investigated by qPCR. Fitness and stability of the revertant were investigated by growth measurements, competition and serial transfer.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The VVESwe-R isolate gained high-level vancomycin (MIC &gt;256\u2009mg\/L) and teicoplanin resistance (MIC\u200a=\u200a8\u2009mg\/L). VVESwe-S has a 5\u2032-truncated vanR activator sequence and the VVESwe-R has in addition acquired a 44\u2009bp deletion upstream of vanHAX in a region containing alternative putative constitutive promoters. In VVESwe-R the vanHAX-operon is constitutively expressed at a level comparable to the non-induced prototype E. faecium BM4147 strain. The vanHAX operon of VVESwe is located on an Inc18-like plasmid, which has a 3\u20134-fold higher copy number in VVESwe-R compared with VVESwe-S. Resistance has a low fitness cost and the vancomycin MIC of VVESwe-R decreased during in vitro serial culture without selection. The reduction in MIC was associated with a decreased vanA-plasmid copy number.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our data support a mechanism by which vancomycin-susceptible VVE strains may revert to a resistant phenotype through the use of an alternative, constitutive, vanR-activator-independent promoter and a vanA-plasmid copy number increase.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jac\/dkaa541","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T23:53:21Z","timestamp":1607558001000},"page":"876-882","source":"Crossref","is-referenced-by-count":24,"title":["Alternative vanHAX<\/i> promoters and increased vanA<\/i>-plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium<\/i>"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8605-6296","authenticated-orcid":false,"given":"Theresa Maria","family":"Wagner","sequence":"first","affiliation":[{"name":"Research group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-6315","authenticated-orcid":false,"given":"Jessin","family":"Janice","sequence":"additional","affiliation":[{"name":"Research group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Troms\u00f8, 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audun","family":"Sivertsen","sequence":"additional","affiliation":[{"name":"Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North-Norway, Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingegerd","family":"Sj\u00f6gren","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Infection Control, Hospital of Halland, Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnfinn","family":"Sundsfjord","sequence":"additional","affiliation":[{"name":"Research group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Troms\u00f8, 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-0497","authenticated-orcid":false,"given":"Kristin","family":"Hegstad","sequence":"additional","affiliation":[{"name":"Research group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Troms\u00f8, 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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"2021031209281354800_dkaa541-B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.drup.2018.10.002","article-title":"Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: towards a common 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