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The reversion of VVE-S to a resistant phenotype was assessed by exposure to increasing vancomycin concentrations, and the revertant isolates were used in filter mating experiments. qPCR was used to analyze the plasmid copy number.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Eleven putative VVE-S were selected. WGS revealed two categories of <jats:italic>vanA<\/jats:italic> cluster plasmid located: the first type showed the lack of <jats:italic>vanR<\/jats:italic>, the deletion of <jats:italic>vanS<\/jats:italic>, and an intact <jats:italic>vanH<\/jats:italic>\/<jats:italic>vanA<\/jats:italic>\/<jats:italic>vanX<\/jats:italic> cluster; the second type was devoid of both <jats:italic>vanR<\/jats:italic> and <jats:italic>vanS<\/jats:italic> and showed a deletion of 544-bp at the 5\u2032-end of the <jats:italic>vanH<\/jats:italic>. Strains (<jats:italic>n<\/jats:italic>\u2009=\u20097) carrying the first type of <jats:italic>vanA<\/jats:italic> cluster were considered VVE-S and were able to regain a resistance phenotype (VVE-R) in the presence of vancomycin, due to a 44-bp deletion in the promoter region of <jats:italic>vanH\/vanA\/vanX<\/jats:italic>, causing its constitutive expression. VVE-R strains were not able to transfer resistance by conjugation, and the resistance phenotype was unstable: after 11\u00a0days of growth without selective pressure, the revertants were still resistant but showed a lower vancomycin MIC. A higher plasmid copy number in the revertant strains was probably related to the resistance phenotype.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We highlight the importance of VVE transition to VRE under vancomycin therapy resulting in a potential failure treatment. We also report the first-time identification of VVE-S isolates <jats:italic>pstS<\/jats:italic>-null belonging to ST1478.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10096-024-04768-0","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T21:22:33Z","timestamp":1706736153000},"page":"673-682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy"],"prefix":"10.1007","volume":"43","author":[{"given":"Sonia Nina","family":"Coccitto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Cinthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Simoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Pocognoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Zeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Mazzariol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Morroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Mingoia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Giovanetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-3908","authenticated-orcid":false,"given":"Andrea","family":"Brenciani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Vignaroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"4768_CR1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/nrmicro2761","volume":"10","author":"CA Arias","year":"2012","unstructured":"Arias CA, Murray BE (2012) The rise of the Enterococcus: beyond vancomycin resistance. 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