{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:15:40Z","timestamp":1790702140299,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of\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            , but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated\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            were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-\n            <jats:italic>N<\/jats:italic>\n            -oxide (DMPO) as spin traps.\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            killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP\u00b7). Lysate pretreatment with the O\n            <jats:sub>2<\/jats:sub>\n            \u00b7\n            <jats:sup>\u2212<\/jats:sup>\n            and \u00b7OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP\u00b7 formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP\u00b7 did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for \u00b7OH and O\n            <jats:sub>2<\/jats:sub>\n            \u00b7\n            <jats:sup>\u2212<\/jats:sup>\n            , with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O\n            <jats:sub>2<\/jats:sub>\n            \u00b7\n            <jats:sup>\u2212<\/jats:sup>\n            -mediated mechanisms producing \u00b7OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that \u00b7OH was generated through these mechanisms and that it participated at least in part in\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            killing by the drug.\n          <\/jats:p>","DOI":"10.1128\/aac.03169-14","type":"journal-article","created":{"date-parts":[[2014,10,7]],"date-time":"2014-10-07T07:44:04Z","timestamp":1412667844000},"page":"7527-7533","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"58","author":[{"given":"Giovanni","family":"Piccaro","sequence":"first","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Pietraforte","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Giannoni","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mustazzolu","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfranco","family":"Fattorini","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01087-08"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00754-12"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00756-12"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.10-13R"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.03.008"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.01.002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2898"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203735109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232751"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232688"},{"key":"e_1_3_2_14_2","first-page":"27","volume-title":"Critical reviews of oxidative stress and aging: advances in basic science, diagnostics and intervention","author":"Buettner GR","year":"2003","unstructured":"BuettnerGRMasonR. 2003. 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