{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T06:26:05Z","timestamp":1784442365385,"version":"3.55.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:p>\n                    Although vancomycin heteroresistance exists in enterococci, it is not easily detected using routine methods and the mechanism is not clearly understood. In this study, we characterized the molecular mechanism underlying vancomycin heteroresistance in a clinical\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    -type\n                    <jats:italic toggle=\"yes\">Enterococcus faecium<\/jats:italic>\n                    strain. The original\n                    <jats:italic toggle=\"yes\">E. faecium<\/jats:italic>\n                    isolate, hVREm7, was susceptible to vancomycin by broth microdilution and Etest. However, vancomycin-resistant subcolonies were present within the Etest zone of inhibition. Three passages of hVREm7 were carried out to eliminate the possibility of contamination. hVREm7 and three resistant variants were selected to study the heteroresistance mechanism. Sequence analysis revealed that all four strains contained an unaltered\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    cluster. Southern blot analysis showed that\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    was present both chromosomally and extrachromosomally in the three variants, but only extrachromosomally in hVREm7. The size of the\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    -bearing extrachromosomal DNA fragments in the three variants was larger than that in hVREm7, indicating a variation of\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    gene amplification in the variants. Consistently,\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    copy number and expression level were increased in variant strain VREm7-1. These results suggest that partial or complete amplification\/transfer of the\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    gene cluster by an as-yet-unidentified mechanism leads to increased copy number and augmented expression of the\n                    <jats:italic toggle=\"yes\">vanM<\/jats:italic>\n                    gene, which contribute to the transformation of vancomycin-heteroresistant\n                    <jats:italic toggle=\"yes\">E. faecium<\/jats:italic>\n                    into high-level vancomycin-resistant variants.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2019.0321","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T15:14:25Z","timestamp":1579274065000},"page":"776-782","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Vancomycin Heteroresistance in\n                    <i>vanM<\/i>\n                    -type\n                    <i>Enterococcus faecium<\/i>"],"prefix":"10.1177","volume":"26","author":[{"given":"Ying","family":"Zhou","sequence":"first","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, China."},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minggui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, China."},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.026385-0"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.01.006"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2014.67"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198807213190307"},{"key":"e_1_3_5_6_2","unstructured":"CDC's Antibiotic Resistance Threats in the United States 2019. Centers for Disease Control and Prevention Department of Health US and Services Human. https:\/\/www.cdc.gov\/drugresistance\/biggest-threats.html#van (accessed January13 2020)."},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.03.003"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks469"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01710-09"},{"key":"e_1_3_5_10_2","volume-title":"vanM","author":"Chen C.","unstructured":"Chen C., , Sun J., , Guo Y., , Lin D., , Guo Q., , Hu F., , Zhu D., , Xu X., , and Wang M.. 2015. High prevalence of vanM. in vancomycin-resistant, Enterococcus faecium, isolates from Shanghai, China. Antimicrob. Agents Chemother. 59: 7795\u2013, 7798."},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.01.003"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.05524-11"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-14"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.9.3379-3381.2001"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.08.007"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00712-08"},{"key":"e_1_3_5_17_2","unstructured":"Clinical and Laboratory Standards Institute. 2018. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. 11th ed. CLSI M07. Clinical and Laboratory Standards Institute Wayne PA."},{"key":"e_1_3_5_18_2","unstructured":"Clinical and Laboratory Standards Institute. 2018. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. CLSI M100\u2013M128. Clinical and Laboratory Standards Institute Wayne PA."},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.1.117-127.1993"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.9.2233-2239.1995"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0097-8485(01)00099-7"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(01)00091-3"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0342-0"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1581-1585.2006"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00088-17"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl302"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02007-17"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku828"}],"container-title":["Microbial Drug Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/mdr.2019.0321","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2019.0321","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2019.0321","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:36:36Z","timestamp":1777667796000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/mdr.2019.0321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7,1]]}},"alternative-id":["10.1089\/mdr.2019.0321"],"URL":"https:\/\/doi.org\/10.1089\/mdr.2019.0321","relation":{},"ISSN":["1076-6294","1931-8448"],"issn-type":[{"value":"1076-6294","type":"print"},{"value":"1931-8448","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,1]]}}}