{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:31:54Z","timestamp":1790937114119,"version":"4.1.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T00:00:00Z","timestamp":1477353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Brazilian National Council of Scientific and Technological Development","award":["237267\/2012-8"],"award-info":[{"award-number":["237267\/2012-8"]}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI095208"],"award-info":[{"award-number":["AI095208"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF-GRFP DGE-1321846"],"award-info":[{"award-number":["NSF-GRFP DGE-1321846"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,11,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Heme oxygenase-1 (HO-1) is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX), a well-characterized HO-1 enzymatic inhibitor, to mice during acute\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            infection\n            <jats:italic>.<\/jats:italic>\n            These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            There is no reliable vaccine against tuberculosis (TB), and conventional antibiotic therapy is administered over at least 6\u00a0months. This prolonged treatment period can lead to noncompliance resulting in relapsed infection as well as the emergence of multidrug resistance. Thus, there is an urgent need for improved therapeutic regimens that can more rapidly and efficiently control\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            in infected patients. Here, we describe a potential strategy for treating TB based on pharmacological inhibition of the host heme-degrading enzyme HO-1. This approach results in significantly reduced bacterial burdens in mice, and when administered in conjunction with conventional antibiotic therapy, leads to faster, more effective pathogen clearance without detectable direct effects on the mycobacteria themselves. Interestingly, the effects of HO-1 inhibition on\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            infection\n            <jats:italic>in vivo<\/jats:italic>\n            are dependent on the presence of an intact host immune system. These observations establish mammalian HO-1 as a potential target for host-directed therapy of TB.\n          <\/jats:p>","DOI":"10.1128\/mbio.01675-16","type":"journal-article","created":{"date-parts":[[2016,10,26]],"date-time":"2016-10-26T02:08:19Z","timestamp":1477447699000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection\n            <i>In Vivo<\/i>\n            by a Mechanism Dependent on T Lymphocytes"],"prefix":"10.1128","volume":"7","author":[{"given":"Diego L.","family":"Costa","sequence":"first","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaranjani","family":"Namasivayam","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo P.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriti","family":"Arora","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara R.","family":"Mittereder","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoudou","family":"Maiga","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena I.","family":"Boshoff","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Clifton E.","family":"Barry","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia W.","family":"Goulding","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA"},{"name":"Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"},{"name":"Unidade de Medicina Investigativa, Laborat\u00f3rio Integrado de Microbiologia e Imunorregula\u00e7\u00e3o, Instituto Pesquisas Gon\u00e7alo Moniz, Fiocruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research, Instituto Brasileiro para a Investiga\u00e7\u00e3o da Tuberculose, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2015","author":"WHO","year":"2015","unstructured":"WHO. 2015. Global tuberculosis report 2015. WHO, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12255"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105600"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.03.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802274200"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062618"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500942"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00251-13"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.116368"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272138"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071367"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00984.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500434"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00115"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0302-240"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1586"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58525"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403104"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103072"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12578"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00721-13"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01298.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2015.01.004"},{"key":"e_1_3_3_26_2","first-page":"485","article-title":"Sn-protoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO incompatibility","volume":"81","author":"Kappas A","year":"1988","unstructured":"Kappas A, Drummond GS, Manola T, Petmezaki S, Valaes T. 1988. Sn-protoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO incompatibility. Pediatrics 81:485\u2013497.","journal-title":"Pediatrics"}],"container-title":["mBio"],"original-title":[],"contributor":[{"given":"Stefan","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]},{"given":"Thomas","family":"Hawn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]}],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01675-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01675-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:10:56Z","timestamp":1646705456000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01675-16"}},"subtitle":[],"editor":[{"given":"Barry R.","family":"Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,11,2]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,11,2]]}},"alternative-id":["10.1128\/mBio.01675-16"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01675-16","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,2]]},"assertion":[{"value":"2016-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01675-16"}}