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We encountered one clinical\n              <jats:italic>Enterococcus faecium<\/jats:italic>\n              strain, SRR12, that carried a complete\n              <jats:italic>vanM<\/jats:italic>\n              gene cluster but was determined as susceptible to vancomycin using the broth microdilution method. However, distinct subcolonies appeared within the clear zone of inhibition in the E-test assay, one of which, named SRR12-v1, showed high-level resistance to vancomycin. SRR12 was confirmed as heteroresistant to vancomycin using population analysis profiling and displayed \u201crevive\u201d growth curves with a lengthy lag phase of over 13 hours when exposed to 2\u201332 mg\/L vancomycin. The resistant subcolony SRR12-v1 was found to carry an identical\n              <jats:italic>vanM<\/jats:italic>\n              gene cluster to that of SRR12 but a significantly increased\n              <jats:italic>vanM<\/jats:italic>\n              copy number in the genome. Long-read whole genome sequencing revealed that a one-copy\n              <jats:italic>vanM<\/jats:italic>\n              gene cluster was located on a pELF1-like linear plasmid in SRR12. In comparison, tandem amplification of the\n              <jats:italic>vanM<\/jats:italic>\n              gene cluster jointed with IS\n              <jats:italic>1216E<\/jats:italic>\n              was seated on a linear plasmid in the genome of SRR12-v1. These amplifications of the\n              <jats:italic>vanM<\/jats:italic>\n              gene cluster were demonstrated as unstable and would decrease accompanied by fitness reversion after serial passaging for 50 generations under increasing vancomycin pressure or without antibiotic pressure but were relatively stable under constant vancomycin pressure. Further,\n              <jats:italic>vanM<\/jats:italic>\n              resistance in resistant variants was verified to be carried by conjugative plasmids with variable sizes using conjugation assays and S1-pulsed field gel electrophoresis blotting, suggesting the instability\/flexibility of\n              <jats:italic>vanM<\/jats:italic>\n              cluster amplification in the genome and an increased risk of\n              <jats:italic>vanM<\/jats:italic>\n              resistance dissemination.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01159-23","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T13:03:03Z","timestamp":1710939783000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Vancomycin heteroresistance caused by unstable tandem amplifications of the\n            <i>vanM<\/i>\n            gene cluster on linear conjugative plasmids in a clinical\n            <i>Enterococcus faecium<\/i>"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7124-3041","authenticated-orcid":false,"given":"Lingyan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China"},{"name":"Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemu","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-1713","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 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