{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:54:37Z","timestamp":1793170477881,"version":"4.5.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The impermeability of the outer membrane in combination with drug efflux are major determinants of the natural drug resistance of mycobacteria. \u03b2-Lactams are the most widely used antibiotics for treatment of bacterial infections. However, it is unknown how \u03b2-lactams enter\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    and whether efflux pumps exist that can export these drugs out of the cell. To identify the molecular mechanisms of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    resistance to \u03b2-lactams, a library of 7,500 transposon mutants was generated in the model organism\n                    <jats:italic>Mycobacterium bovis<\/jats:italic>\n                    BCG. Thirty-three unique insertion sites were determined that conferred medium or high-level (\u22652,000 \u03bcg\/ml) resistance to ampicillin. Three mutants in sulfolipid synthesis or transport were highly resistant to ampicillin, indicating an indirect effect of the lipid composition on the outer membrane permeability of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    BCG to ampicillin. Mutants with insertions in genes encoding surface molecules such as PPE proteins or lipoarabinomannan were also completely resistant to ampicillin, thus suggesting a lack of transport across the outer membrane. Insertion of the transposon in front of\n                    <jats:italic>bcg0231<\/jats:italic>\n                    increased transcription of the gene and concomitantly the resistance of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    BCG to ampicillin, streptomycin, and chloramphenicol by 32- to 64-fold. Resistance to vancomycin and tetracycline was increased four- to eightfold. Bcg0231 and Rv0194 are almost identical ATP-binding cassette transporters. Expression of\n                    <jats:italic>rv0194<\/jats:italic>\n                    significantly reduced accumulation of ethidium bromide and conferred multidrug resistance to\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    . Both effects were abrogated in the presence of the efflux pump inhibitor reserpine. These results demonstrate that Rv0194 is a novel multidrug efflux pump of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/aac.00298-08","type":"journal-article","created":{"date-parts":[[2008,5,5]],"date-time":"2008-05-05T20:34:22Z","timestamp":1210019662000},"page":"2503-2511","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":139,"title":["Identification of a Novel Multidrug Efflux Pump of\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1128","volume":"52","author":[{"given":"Olga","family":"Danilchanka","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, 609 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, Alabama 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mailaender","sequence":"additional","affiliation":[{"name":"Lehrstuhl fu\u0308r Mikrobiologie, Friedrich-Alexander-Universita\u0308t Erlangen-Nu\u0308rnberg, Staudtstr. 5, D-91058 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Niederweis","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, 609 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, Alabama 35294"},{"name":"Lehrstuhl fu\u0308r Mikrobiologie, Friedrich-Alexander-Universita\u0308t Erlangen-Nu\u0308rnberg, Staudtstr. 5, D-91058 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82095-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.22.5836-5843.1998"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00509-07"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.9.2568-2573.1998"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608654104"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2000.tb00550.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.64.070195.000333"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04183.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0005-2736(92)90308-9","volume":"1111","year":"1992","unstructured":"Chakrabarti, A. C., and D. W. Deamer. 1992. Permeability of lipid bilayers to amino acids and phosphate. Biochim. Biophys. Acta1111:171-177.","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2620"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.2816-2821.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00388-06"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1030024100"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04007.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2005.00002.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.1931"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3492-3501.2005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01046-07"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27629-0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.2.362-366.1998"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1039\/b616817p","volume":"24","year":"2007","unstructured":"Gokhale, R. S., P. Saxena, T. Chopra, and D. Mohanty. 2007. Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat. Prod. Rep.24:267-277.","journal-title":"Nat. Prod. Rep."},{"key":"e_1_3_2_23_2","first-page":"415","volume":"100","year":"2006","unstructured":"Harries, A. D., and C. Dye. 2006. Tuberculosis. Ann. Trop. Med. Parasitol.100:415-431.","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.2.273"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01474-06"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2413-2417.2003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00712-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408410091154228"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464020-00004"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.7.2415-2423.2004"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00001-07"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1099\/mic.0.2007\/007864-0","volume":"153","year":"2007","unstructured":"Lynett, J., and R. W. Stokes. 2007. Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages. Microbiology153:3133-3140.","journal-title":"Microbiology"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26902-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990855s"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(00)00243-5"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0109515"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.3.1004-1012.1995"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2005.12.002"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1183\/09031936.00001307","volume":"29","year":"2007","unstructured":"Migliori, G. B., R. Loddenkemper, F. Blasi, and M. C. Raviglione. 2007. 125 years after Robert Koch's discovery of the tubercle bacillus: the new XDR-TB threat. Is \u201cscience\u201d enough to tackle the epidemic? Eur. Respir. J.29:423-427.","journal-title":"Eur. Respir. J."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2000.0247"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10955"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1464"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.12.007"},{"key":"e_1_3_2_44_2","first-page":"2200","volume":"61","year":"2004","unstructured":"Poole, K. 2004. Resistance to beta-lactam antibiotics. Cell Mol. Life Sci.61:2200-2223.","journal-title":"Cell Mol. Life Sci."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1998.tb12803.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.6.1174"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.10.6048-6053.1990"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00058-06"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1645"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(04)00017-5"},{"key":"e_1_3_2_51_2","unstructured":"Tuberculosis. 2008"},{"key":"e_1_3_2_52_2","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1016\/j.micinf.2006.04.008","volume":"8","year":"2006","unstructured":"Stadthagen, G., M. Jackson, P. Charles, F. Boudou, N. Barilone, M. Huerre, P. Constant, A. Liav, I. Bottova, J. Nigou, T. Brando, G. Puzo, M. Daffe, P. Benjamin, S. Coade, R. S. Buxton, R. E. Tascon, A. Rae, B. D. Robertson, D. B. Lowrie, D. B. Young, B. Gicquel, and R. Griffin. 2006. Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives. Microbes Infect.8:2245-2253.","journal-title":"Microbes Infect."},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02394.x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04878.x"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4163-4170.2004"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.362"},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1136\/thorax.55.11.962","volume":"55","year":"2000","unstructured":"White, V. L., and J. Moore-Gillon. 2000. Resource implications of patients with multidrug resistant tuberculosis. Thorax55:962-963.","journal-title":"Thorax"},{"key":"e_1_3_2_58_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.cbpa.2003.08.004","volume":"7","year":"2003","unstructured":"Wright, G. D. 2003. Mechanisms of resistance to antibiotics. Curr. Opin. Chem. Biol.7:563-569.","journal-title":"Curr. Opin. Chem. Biol."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00298-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00298-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T14:50:10Z","timestamp":1645455010000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00298-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7]]},"references-count":57,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["10.1128\/AAC.00298-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.00298-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7]]},"assertion":[{"value":"2008-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}