{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:29:52Z","timestamp":1790299792525,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            New drugs and drugs with a novel mechanism of action are desperately needed to shorten the duration of tuberculosis treatment, to prevent the emergence of drug resistance, and to treat multiple-drug-resistant strains 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            . Recently, there has been renewed interest in clofazimine (CFZ). In this study, we utilized the C3HeB\/FeJ mouse model, possessing highly organized, hypoxic pulmonary granulomas with caseous necrosis, to evaluate CFZ monotherapy in comparison to results with BALB\/c mice, which form only multifocal, coalescing cellular aggregates devoid of caseous necrosis. While CFZ treatment was highly effective in BALB\/c mice, its activity was attenuated in the lungs of C3HeB\/FeJ mice. This lack of efficacy was directly related to the pathological progression of disease in these mice, since administration of CFZ prior to the formation of hypoxic, necrotic granulomas reconstituted bactericidal activity in this mouse strain. These results support the continued use of mouse models of tuberculosis infection which exhibit a granulomatous response in the lungs that more closely resembles the pathology found in human disease.\n          <\/jats:p>","DOI":"10.1128\/aac.02565-14","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T03:36:16Z","timestamp":1399347376000},"page":"4026-4034","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":108,"title":["Limited Activity of Clofazimine as a Single Drug in a Mouse Model of Tuberculosis Exhibiting Caseous Necrotic Granulomas"],"prefix":"10.1128","volume":"58","author":[{"given":"Scott M.","family":"Irwin","sequence":"first","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Gruppo","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Brooks","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Gilliland","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scherman","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Reichlen","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Department of Microbiology, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Leistikow","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Department of Microbiology, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kramnik","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine, Department of Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Nuermberger","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin I.","family":"Voskuil","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Department of Microbiology, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne J.","family":"Lenaerts","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1333467"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-publhealth-031912-114431"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/1791013a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02945619"},{"key":"e_1_3_2_6_2","first-page":"107","article-title":"The experimental properties of G 30 320 (B 663)\u2014a new anti-leprotic agent","volume":"40","author":"Vischer WA","year":"1969","unstructured":"VischerWA. 1969. The experimental properties of G 30 320 (B 663)\u2014a new anti-leprotic agent. Lepr. Rev. 40:107\u2013110.","journal-title":"Lepr. Rev."},{"key":"e_1_3_2_7_2","first-page":"226","volume-title":"Proceedings of the 14th V.A.-A.V. Conference on Tuberculosis","author":"Schmidt L","year":"1955","unstructured":"SchmidtLHoffmanRJollyP. 1955. Induced pulmonary tuberculosis in the rhesus monkey: its usefulness in evaluating chemotherapeutic agents. Proceedings of the 14th V.A.-A.V. Conference on Tuberculosis, p 226\u2013231. Veterans Administration, Atlanta, GA."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/151.4.1083"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00699-11"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm300828h"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0077OC"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0753OC"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05293-11"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00384-12"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis034"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1974.23.1110"},{"key":"e_1_3_2_17_2","first-page":"1","article-title":"Electron microscope studies of the antileprosy drug B663 (clofazimine; Lamprenel)","volume":"42","author":"McDougall AC","year":"1974","unstructured":"McDougallAC. 1974. Electron microscope studies of the antileprosy drug B663 (clofazimine; Lamprenel). Int. J. Lepr. Other Mycobact. Dis. 42:1\u201312.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1980.tb05697.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01797865"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-0903"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017550"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470846526.ch9"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03419"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00217-12"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir786"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.6.2294-2301.2005"},{"key":"e_1_3_2_27_2","first-page":"181","article-title":"Immune responses in animal models","volume":"215","author":"Orme IM","year":"1996","unstructured":"OrmeIM. 1996. Immune responses in animal models. Curr. Top. Microbiol. Immunol. 215:181\u2013196.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/am.24.3.311-317.1972"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00926-09"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8479(97)90016-2"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.2062-2069.1996"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081075"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(93)90086-E"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(86)90033-0"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.21.5.693"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004009"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2249"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2000.00933.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.200501"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232751"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232688"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00055-06"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.11.0752"},{"key":"e_1_3_2_44_2","first-page":"46","volume-title":"Chemotherapy of tuberculosis","author":"Barry V","year":"1964","unstructured":"BarryV. 1964. The development of chemotherapeutic agent for tuberculosis, p 46\u201364. In BarryV (ed), Chemotherapy of tuberculosis. Butterworth & Co., London, England."},{"key":"e_1_3_2_45_2","first-page":"3","article-title":"The antimycobacterial activity of B 663","volume":"36","author":"Barry VC","year":"1965","unstructured":"BarryVCConaltyML. 1965. The antimycobacterial activity of B 663. Lepr. Rev. 36:3\u20137.","journal-title":"Lepr. Rev."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02026384"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047494"},{"key":"e_1_3_2_48_2","first-page":"541","article-title":"Clofazimine crystals in alveolar macrophages from a patient with the acquired immunodeficiency syndrome","volume":"116","author":"Sandler ED","year":"1992","unstructured":"SandlerEDNgVLHadleyWK. 1992. Clofazimine crystals in alveolar macrophages from a patient with the acquired immunodeficiency syndrome. Arch. Pathol. Lab. Med. 116:541\u2013543.","journal-title":"Arch. Pathol. Lab. Med."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/43.5.615"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac1029049"},{"key":"e_1_3_2_51_2","unstructured":"Global Alliance for TB Drug Development. 2013. Evaluation of early bactericidal activity in pulmonary tuberculosis with clofazimine TMC207 PA-824 pyrazinamide (NC-003); NCT01691534. http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01691534."},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-9792(08)70038-6"},{"key":"e_1_3_2_53_2","first-page":"9","article-title":"Pharmacokinetics of clofazimine in healthy volunteers","volume":"55","author":"Schaad-Lanyi Z","year":"1987","unstructured":"Schaad-LanyiZDieterleWDuboisJPTheobaldWVischerW. 1987. Pharmacokinetics of clofazimine in healthy volunteers. Int. J. Lepr. Other Mycobact. Dis. 55:9\u201315.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02565-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02565-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:48:40Z","timestamp":1645483720000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02565-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1128\/AAC.02565-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.02565-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7]]},"assertion":[{"value":"2014-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-04-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}