{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:05:24Z","timestamp":1791273924722,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T00:00:00Z","timestamp":1088640000000},"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":[[2004,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The\n            <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n            genome contains many genes encoding putative drug efflux pumps. Yet with the exception of\n            <jats:italic>lfrA<\/jats:italic>\n            , it is not clear whether these genes contribute to the intrinsic drug resistance of this organism. We showed first by reverse transcription (RT)-PCR that several of these genes, including\n            <jats:italic>lfrA<\/jats:italic>\n            as well as the homologues of\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            Rv1145, Rv1146, Rv1877, Rv2846c (\n            <jats:italic>efpA<\/jats:italic>\n            ), and Rv3065 (\n            <jats:italic>mmr<\/jats:italic>\n            and\n            <jats:italic>emrE<\/jats:italic>\n            ), were expressed at detectable levels in the strain mc\n            <jats:sup>2<\/jats:sup>\n            155. Null mutants each carrying an in-frame deletion of these genes were then constructed in\n            <jats:italic>M. smegmatis<\/jats:italic>\n            . The deletions of the\n            <jats:italic>lfrA<\/jats:italic>\n            gene or\n            <jats:italic>mmr<\/jats:italic>\n            homologue rendered the mutant more susceptible to multiple drugs such as fluoroquinolones, ethidium bromide, and acriflavine (two- to eightfold decrease in MICs). The deletion of the\n            <jats:italic>efpA<\/jats:italic>\n            homologue also produced increased susceptibility to these agents but unexpectedly also resulted in decreased susceptibility to rifamycins, isoniazid, and chloramphenicol (two- to fourfold increase in MICs). Deletion of the Rv1877 homologue produced some increased susceptibility to ethidium bromide, acriflavine, and erythromycin. The upstream region of\n            <jats:italic>lfrA<\/jats:italic>\n            contained a gene encoding a putative TetR family transcriptional repressor, dubbed LfrR. The deletion of\n            <jats:italic>lfrR<\/jats:italic>\n            elevated the expression of\n            <jats:italic>lfrA<\/jats:italic>\n            and produced higher resistance to multiple drugs. Multidrug-resistant single-step mutants, independent of LfrA and attributed to a yet-unidentified drug efflux pump (here called LfrX), were selected in vitro and showed decreased accumulation of norfloxacin, ethidium bromide, and acriflavine in intact cells. Finally, use of isogenic \u03b2-lactamase-deficient strains showed the contribution of LfrA and LfrX to resistance to certain \u03b2-lactams in\n            <jats:italic>M. smegmatis<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.48.7.2415-2423.2004","type":"journal-article","created":{"date-parts":[[2004,6,23]],"date-time":"2004-06-23T22:18:08Z","timestamp":1088029088000},"page":"2415-2423","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":210,"title":["Efflux Pump-Mediated Intrinsic Drug Resistance in\n            <i>Mycobacterium smegmatis<\/i>"],"prefix":"10.1128","volume":"48","author":[{"given":"Xian-Zhi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nikaido","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072105"},{"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":"crossref","first-page":"23","DOI":"10.1016\/0378-1119(96)00202-8","volume":"176","year":"1996","unstructured":"Ainsa, J. A., C. Martin, M. Cabeza, F. De la Cruz, and M. V. Mendiola. 1996. Construction of a family of Mycobacterium\/Escherichia coli shuttle vectors derived from pAL5000 and pACYC184: their use for cloning an antibiotic-resistance gene from Mycobacterium fortuitum.Gene176:23-26.","journal-title":"Gene"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2000.tb00550.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.64.070195.000333"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.116.3003.45"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2620"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020615"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1006\/bbrc.1999.0357","volume":"256","year":"1999","unstructured":"Choudhuri, B. S., S. Sen, and P. Chakrabarti. 1999. Isoniazid accumulation in Mycobacterium smegmatis is modulated by proton motive force-driven and ATP-dependent extrusion systems. Biochem. Biophys. Res. Commun.256:682-684.","journal-title":"Biochem. Biophys. Res. 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Some common methods in mycobacterial genetics, p. 313-320. In G. F. Hatfull and W. R. Jacobs, Jr. (ed.), Molecular genetics of mycobacteria. ASM Press, Washington, D.C.","journal-title":"Molecular genetics of mycobacteria"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.8.1742"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464020-00004"},{"key":"e_1_3_2_24_2","first-page":"388","volume":"19","year":"1988","unstructured":"Li, X.-Z., Y.-S. Wang, and Z.-N. He. 1988. Alteration of permeability of bacterial envelope barrier in rifamdin-resistant Mycobacterium tuberculosis.J. West. Chin. Univ. Med. Sci.19:388-391.","journal-title":"J. West. Chin. Univ. Med. 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