{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:13:20Z","timestamp":1791422000191,"version":"4.3.3"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[1999,3,1]],"date-time":"1999-03-01T00:00:00Z","timestamp":920246400000},"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":[[1999,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n            , the causative agent of melioidosis, is intrinsically resistant to a wide range of antimicrobial agents including \u03b2-lactams, aminoglycosides, macrolides, and polymyxins. We used Tn\n            <jats:italic>5<\/jats:italic>\n            -OT182 to mutagenize\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            to identify the genes involved in aminoglycoside resistance. We report here on the identification of AmrAB-OprA, a multidrug efflux system in\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            which is specific for both aminoglycoside and macrolide antibiotics. We isolated two transposon mutants, RM101 and RM102, which had 8- to 128-fold increases in their susceptibilities to the aminoglycosides streptomycin, gentamicin, neomycin, tobramycin, kanamycin, and spectinomycin. In addition, both mutants, in contrast to the parent, were susceptible to the macrolides erythromycin and clarithromycin but not to the lincosamide clindamycin. Sequencing of the DNA flanking the transposon insertions revealed a putative operon consisting of a resistance, nodulation, division-type transporter, a membrane fusion protein, an outer membrane protein, and a divergently transcribed regulator protein. Consistent with the presence of an efflux system, both mutants accumulated [\n            <jats:sup>3<\/jats:sup>\n            H]dihydrostreptomycin, whereas the parent strain did not. We constructed an\n            <jats:italic>amr<\/jats:italic>\n            deletion strain,\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            DD503, which was hypersusceptible to aminoglycosides and macrolides and which was used successfully in allelic exchange experiments. These results suggest that an efflux system is a major contributor to the inherent high-level aminoglycoside and macrolide resistance found in\n            <jats:italic>B. pseudomallei<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.43.3.465","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:19Z","timestamp":1539045259000},"page":"465-470","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":254,"title":["Efflux-Mediated Aminoglycoside and Macrolide Resistance in\n            <i>Burkholderia pseudomallei<\/i>"],"prefix":"10.1128","volume":"43","author":[{"given":"Richard A.","family":"Moore","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna","family":"Reckseidler","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ania","family":"Weissman","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Woods","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.853"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S095026889600739X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.7164\/antibiotics.28.696","article-title":"Streptomycin accumulation in susceptible and resistant strains of Escherichia coli and Pseudomonas aeruginosa.","volume":"28","author":"Bryan L. E.","year":"1976","unstructured":"Bryan L. E. Van den Elzen H. M. Streptomycin accumulation in susceptible and resistant strains of Escherichia coli and Pseudomonas aeruginosa. J. Antibiot. 28 1976 696 703","journal-title":"J. Antibiot."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.5.890"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.01521.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.4.1.52"},{"key":"e_1_3_2_9_2","unstructured":"Dance\n              D. A. B.\n          Melioidosis\n          Manson\u2019s tropical diseases\n          20th ed.\n              Cook\n              G. C.\n          1996\n          925\n          930\n          The W. B. Saunders Co. Ltd.\n          London England"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(97)01033-0"},{"key":"e_1_3_2_11_2","unstructured":"DeShazer D. P. J. Brett and D. E. Woods. 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Approved standard M7-T2.\n          1990\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.20.5853-5859.1996"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.9.2021"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1046\/j.1365-2958.1996.281397.x","article-title":"Overexpression of the mexC-mexD-oprJ efflux operon in nfxB type multidrug-resistant strains of Pseudomonas aeruginosa.","volume":"21","author":"Poole K.","year":"1996","unstructured":"Poole K. Gotoh N. Tsujimoto H. Zhao Q. Wada A. Yamasaki T. Neshat S. Yamagishi J.-I. Li X.-Z. Nishino T. Overexpression of the mexC-mexD-oprJ efflux operon in nfxB type multidrug-resistant strains of Pseudomonas aeruginosa. Mol. Microbiol. 21 1996 713 724","journal-title":"Mol. 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