{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:04:06Z","timestamp":1791950646578,"version":"4.3.4"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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":[[2011,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Therapeutic options for tuberculosis (TB) are limited and notoriously ineffective despite the wide variety of potent antibiotics available for treating other bacterial infections. We investigated an approach that enables an expansion of TB therapeutic strategies by using synergistic combinations of drugs. To achieve this, we devised a high-throughput synergy screen (HTSS) of chemical libraries having known pharmaceutical properties, including thousands that are clinically approved. Spectinomycin was used to test the concept that clinically available antibiotics with limited efficacy against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    might be used for TB treatment when coadministered with a synergistic partner compound used as a sensitizer. Screens using\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    revealed many compounds in our libraries that acted synergistically with spectinomycin. Among them, several families of antimicrobial compounds, including macrolides and azoles, were also synergistic against\n                    <jats:italic>M. tuberculosis in vitro<\/jats:italic>\n                    and in a macrophage model of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    infection. Strikingly, each sensitizer identified for synergy with spectinomycin uniquely enhanced the activities of other clinically used antibiotics, revealing a remarkable number of unexplored synergistic drug combinations. HTSS also revealed a novel activity for bromperidol, a butyrophenone used as an antipsychotic drug, which was discovered to be bactericidal and greatly enhanced the activities of several antibiotics and drug combinations against\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . Our results suggest that many compounds in the currently available pharmacopoeia could be readily mobilized for TB treatment, including disease caused by multi- and extensively drug-resistant strains for which there are no effective therapies.\n                  <\/jats:p>","DOI":"10.1128\/aac.00474-11","type":"journal-article","created":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T00:54:39Z","timestamp":1305593679000},"page":"3861-3869","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":177,"title":["Synergistic Drug Combinations for Tuberculosis Therapy Identified by a Novel High-Throughput Screen"],"prefix":"10.1128","volume":"55","author":[{"given":"Santiago","family":"Ram\u00f3n-Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingji","family":"Zheng","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Department of Medicine, University of British Columbia, 2733 Heather Street, Vancouver, BC V5Z 3J5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"Centre for Drug Research and Development, 2259 Lower Mall, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yossef","family":"Av-Gay","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Department of Medicine, University of British Columbia, 2733 Heather Street, Vancouver, BC V5Z 3J5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Roberge","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Drug Research and Development, 2259 Lower Mall, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"},{"name":"Centre for Tuberculosis Research, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"19","article-title":"Extensively resistant tuberculosis (XDR-TB) in Argentina: epidemiology, bacteriology, therapy and outcome","volume":"1","author":"Abbate E.","year":"2007","unstructured":"AbbateE. . 2007. Extensively resistant tuberculosis (XDR-TB) in Argentina: epidemiology, bacteriology, therapy and outcome. Rev. Argentina Med. Respir. 1:19\u201325.","journal-title":"Rev. Argentina Med. Respir"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2007.00825.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00257-10"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.12.019"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.5.505"},{"key":"e_1_3_3_7_2","first-page":"85","article-title":"Handbook of anti-tuberculosis agents","volume":"88","author":"Anonymous","year":"2008","unstructured":"Anonymous. 2008. Handbook of anti-tuberculosis agents. Tuberculosis (Edinb.) 88:85\u2013170.","journal-title":"Tuberculosis (Edinb.)"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.6.1542"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198835060-00004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1169920"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555815929"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2010.01738.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/448645a"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2007.09.004"},{"key":"e_1_3_3_15_2","first-page":"1-86","volume-title":"Residues of some veterinary drugs in animals and foodsFAO Food Nutr. Pap","volume":"41","author":"Cuerpo L.","year":"1994","unstructured":"CuerpoL. LivingstonR. C.. 1994. Spectinomycin. In Residues of some veterinary drugs in animals and foods. Monographs prepared by the Forty-second Meeting of the Joint FAO\/WHO Expert Committee on Food Additives. FAO Food Nutr. Pap. 41:1-86."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01474-06"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600700904"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-6296(02)00126-1"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-9792(08)70038-6"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.25.827"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057109335743"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00272-08"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167498"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70260-3"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.693-715.2004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09657"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.08.026"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-10-2937"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki023"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02428031"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2006.05.005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/130.1.50"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg301"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2009.07.011"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2201"},{"key":"e_1_3_3_37_2","volume-title":"Trobicin (spectinomycin) for injectable suspension prescribing information","author":"Pharmacia & Upjohn Company","year":"2003","unstructured":"Pharmacia & Upjohn Company. 2003. Trobicin (spectinomycin) for injectable suspension prescribing information. Pharmacia & Upjohn Company, Kalamazoo, MI."},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701195262"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki436"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2009.07.003"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012640"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555817886"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1101548"},{"key":"e_1_3_3_44_2","volume-title":"Report: global tuberculosis control","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. Report: global tuberculosis control. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(01)00218-4"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1755"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609370104"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00474-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00474-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:19:21Z","timestamp":1645467561000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00474-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["10.1128\/AAC.00474-11"],"URL":"https:\/\/doi.org\/10.1128\/aac.00474-11","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8]]},"assertion":[{"value":"2011-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}