{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:15:20Z","timestamp":1790900120809,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial resistance to the glycopeptide antibiotic teicoplanin shows some important differences from the closely related compound vancomycin. They are currently poorly understood but may reflect significant differences in the mode of action of each antibiotic.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptomyces coelicolor<\/jats:named-content>\n            possesses a\n            <jats:italic>vanRSJKHAX<\/jats:italic>\n            gene cluster that when expressed confers resistance to both vancomycin and teicoplanin. The resistance to vancomycin is mediated by the enzymes encoded by\n            <jats:italic>vanKHAX<\/jats:italic>\n            , but not by\n            <jats:italic>vanJ. vanHAX<\/jats:italic>\n            effect a reprogramming of peptidoglycan biosynthesis, which is considered to be generic, conferring resistance to all glycopeptide antibiotics. Here, we show that\n            <jats:italic>vanKHAX<\/jats:italic>\n            are not in fact required for teicoplanin resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. coelicolor<\/jats:named-content>\n            , which instead is mediated solely by\n            <jats:italic>vanJ. vanJ<\/jats:italic>\n            is shown to encode a membrane protein oriented with its C-terminal active site exposed to the extracytoplasmic space. VanJ also confers resistance to the teicoplanin-like antibiotics ristocetin and A47934 and to a broad range of semisynthetic teicoplanin derivatives, but not generally to antibiotics or semisynthetic derivatives with vancomycin-like structures.\n            <jats:italic>vanJ<\/jats:italic>\n            homologues are found ubiquitously in streptomycetes and include\n            <jats:italic>staP<\/jats:italic>\n            from the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptomyces toyocaensis<\/jats:named-content>\n            A47934 biosynthetic gene cluster. While overexpression of\n            <jats:italic>staP<\/jats:italic>\n            also conferred resistance to teicoplanin, similar expression of other\n            <jats:italic>vanJ<\/jats:italic>\n            homologues (SCO2255, SCO7017, and SAV5946) did not. The\n            <jats:italic>vanJ<\/jats:italic>\n            and\n            <jats:italic>staP<\/jats:italic>\n            orthologues, therefore, appear to represent a subset of a larger protein family whose members have acquired specialist roles in antibiotic resistance. Future characterization of the divergent enzymatic activity within this new family will contribute to defining the molecular mechanisms important for teicoplanin activity and resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.05869-11","type":"journal-article","created":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T05:36:20Z","timestamp":1326173780000},"page":"1784-1796","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["A Novel Membrane Protein, VanJ, Conferring Resistance to Teicoplanin"],"prefix":"10.1128","volume":"56","author":[{"given":"Gabriela","family":"Novotna","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jeon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.375-381.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.8.2582-2591.1992"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.1.117-127.1993"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)00851-I"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.00617.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.10.2291"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.4401812.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.38.100184.002011"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.781"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00107a007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931492100"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S1074-5521(00)80008-3","article-title":"Binding of glycopeptide antibiotics to a model of a vancomycin-resistant bacterium","volume":"6","author":"Cooper MA","year":"1999","unstructured":"CooperMA WilliamsDH. 1999. 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