{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:16:37Z","timestamp":1792167397034,"version":"4.4.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"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":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The metallo-\u03b2-lactamase NDM-1 is among the most worrisome resistance determinants and is spreading worldwide among Gram-negative bacilli. A bleomycin resistance gene,\n            <jats:italic>ble<\/jats:italic>\n            <jats:sub>MBL<\/jats:sub>\n            , downstream of the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>NDM-1<\/jats:sub>\n            gene has been associated with resistance almost systematically. Here, we characterized the corresponding protein, BRP\n            <jats:sub>MBL<\/jats:sub>\n            , conferring resistance to bleomycin, an antitumoral glycopeptide molecule. We have determined whether the expression of the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>NDM-1<\/jats:sub>\n            -\n            <jats:italic>ble<\/jats:italic>\n            <jats:sub>MBL<\/jats:sub>\n            operon is inducible in the presence of carbapenems and\/or bleomycin-like molecules using quantitative reverse transcription-PCR (qRT-PCR), determination of imipenem and zeocin MICs, and carbapenemase-specific activity assays. We showed that the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>NDM-1<\/jats:sub>\n            -\n            <jats:italic>ble<\/jats:italic>\n            <jats:sub>MBL<\/jats:sub>\n            operon is constitutively expressed. Using electrophoretic mobility shift and DNA protection assays performed with purified glutathione\n            <jats:italic>S<\/jats:italic>\n            -transferase (GST)-BRP\n            <jats:sub>MBL<\/jats:sub>\n            , we demonstrated that BRP\n            <jats:sub>MBL<\/jats:sub>\n            is able to bind and sequester bleomycin-like molecules, thus preventing bleomycin-dependent DNA degradation.\n            <jats:italic>In silico<\/jats:italic>\n            modeling confirmed that the mechanism of action required the dimerization of the BRP\n            <jats:sub>MBL<\/jats:sub>\n            protein in order to sequester bleomycin and prevent DNA damage. BRP\n            <jats:sub>MBL<\/jats:sub>\n            acts specifically on bleomycin-like molecules since cloning and expression of\n            <jats:italic>ble<\/jats:italic>\n            <jats:sub>MBL<\/jats:sub>\n            in\n            <jats:named-content content-type=\"genus-species\">Staphyloccoccus aureus<\/jats:named-content>\n            did not confer cross-resistance to any other antimicrobial glycopeptides such as vancomycin and teicoplanin.\n          <\/jats:p>","DOI":"10.1128\/aac.02413-16","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T02:30:27Z","timestamp":1484015427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Characterization of BRP\n            <sub>MBL<\/sub>\n            , the Bleomycin Resistance Protein Associated with the Carbapenemase NDM"],"prefix":"10.1128","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7384","authenticated-orcid":false,"given":"Laurent","family":"Dortet","sequence":"first","affiliation":[{"name":"Bacteriology-Hygiene unit, Assistance Publique\/H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"EA7361 (Structure, dynamic, function and expression of broad spectrum \u03b2-lactamases), Paris-Sud University, LabEx Lermit, Faculty of Medicine, Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacteriaceae, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Girlich","sequence":"additional","affiliation":[{"name":"EA7361 (Structure, dynamic, function and expression of broad spectrum \u03b2-lactamases), Paris-Sud University, LabEx Lermit, Faculty of Medicine, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laure","family":"Virlouvet","sequence":"additional","affiliation":[{"name":"Bacteriology-Hygiene unit, Assistance Publique\/H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Poirel","sequence":"additional","affiliation":[{"name":"Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Switzerland"},{"name":"INSERM European Unit (LEA Paris, IAME, France), University of Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Nordmann","sequence":"additional","affiliation":[{"name":"Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Switzerland"},{"name":"INSERM European Unit (LEA Paris, IAME, France), University of Fribourg, Switzerland"},{"name":"University hospital and University of Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan I.","family":"Iorga","sequence":"additional","affiliation":[{"name":"Institut de Chimie des Substances Naturelles, CNRS UPR 2301, LabEx LERMIT, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Naas","sequence":"additional","affiliation":[{"name":"Bacteriology-Hygiene unit, Assistance Publique\/H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"EA7361 (Structure, dynamic, function and expression of broad spectrum \u03b2-lactamases), Paris-Sud University, LabEx Lermit, Faculty of Medicine, Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacteriaceae, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"200","article-title":"New antibiotics, bleomycin A and B","volume":"19","author":"Umezawa H","year":"1966","unstructured":"Umezawa H MaedaK TakeuchiT OkamiY. 1966. 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