{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:38:05Z","timestamp":1791776285748,"version":"4.3.4"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"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":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The 1,5-diarylpyrrole derivative BM212 was previously shown to be active against multidrug-resistant clinical isolates and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            residing within macrophages as well as against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium avium<\/jats:named-content>\n            and other atypical mycobacteria. To determine its mechanism of action, we identified the cellular target. Spontaneous\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium smegmatis<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium bovis<\/jats:named-content>\n            BCG, and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            H37Rv mutants that were resistant to BM212 were isolated. By the screening of genomic libraries and by whole-genome sequencing, we found that all the characterized mutants showed mutations in the\n            <jats:italic>mmpL3<\/jats:italic>\n            gene, allowing us to conclude that resistance to BM212 maps to the MmpL3 protein, a member of the MmpL (\n            <jats:italic>m<\/jats:italic>\n            ycobacterial\n            <jats:italic>m<\/jats:italic>\n            embrane\n            <jats:italic>p<\/jats:italic>\n            rotein,\n            <jats:italic>l<\/jats:italic>\n            arge) family. Susceptibility was unaffected by the efflux pump inhibitors reserpine, carbonylcyanide\n            <jats:italic>m<\/jats:italic>\n            -chlorophenylhydrazone, and verapamil. Uptake\/efflux experiments with [\n            <jats:sup>14<\/jats:sup>\n            C]BM212 demonstrated that resistance is not driven by the efflux of BM212. Together, these data strongly suggest that the MmpL3 protein is the cellular target of BM212.\n          <\/jats:p>","DOI":"10.1128\/aac.05270-11","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T05:44:10Z","timestamp":1319521450000},"page":"324-331","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":209,"title":["MmpL3 Is the Cellular Target of the Antitubercular Pyrrole Derivative BM212"],"prefix":"10.1128","volume":"56","author":[{"given":"Valentina","family":"La Rosa","sequence":"first","affiliation":[{"name":"Dipartimento di Genetica e Microbiologia, Universit\u00e0 degli Studi di Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Poce","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA"},{"name":"Istituto Pasteur Fondazione Cenci-Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Universit\u00e0 La Sapienza, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Ortiz","family":"Canseco","sequence":"additional","affiliation":[{"name":"Dipartimento di Genetica e Microbiologia, Universit\u00e0 degli Studi di Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Buroni","sequence":"additional","affiliation":[{"name":"Dipartimento di Genetica e Microbiologia, Universit\u00e0 degli Studi di Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosalia","family":"Pasca","sequence":"additional","affiliation":[{"name":"Dipartimento di Genetica e Microbiologia, Universit\u00e0 degli Studi di Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Biava","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Fondazione Cenci-Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Universit\u00e0 La Sapienza, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikiran M.","family":"Raju","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio Cesare","family":"Porretta","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Fondazione Cenci-Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Universit\u00e0 La Sapienza, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Alfonso","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Fondazione Cenci-Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Universit\u00e0 La Sapienza, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Battilocchio","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Fondazione Cenci-Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Universit\u00e0 La Sapienza, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Javid","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Ioerger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Manetti","sequence":"additional","affiliation":[{"name":"Dipartimento Farmaco Chimico Tecnologico, Universit\u00e0 degli Studi di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Botta","sequence":"additional","affiliation":[{"name":"Dipartimento Farmaco Chimico Tecnologico, Universit\u00e0 degli Studi di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"De Logu","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia Medica, Universit\u00e0 di Cagliari, 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