{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:05:46Z","timestamp":1792569946407,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            strains are less susceptible to tigecycline (previously GAR-936; MIC, 8 \u03bcg\/ml) than many other bacteria (P. J. Petersen, N. V. Jacobus, W. J. Weiss, P. E. Sum, and R. T. Testa, Antimicrob. Agents Chemother. 43:738-744, 1999). To elucidate the mechanism of resistance to tigecycline,\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            PAO1 strains defective in the MexAB-OprM and\/or MexXY (OprM) efflux pumps were tested for susceptibility to tigecycline. Increased susceptibility to tigecycline (MIC, 0.5 to 1 \u03bcg\/ml) was specifically associated with loss of MexXY. Transcription of\n            <jats:italic>mexX<\/jats:italic>\n            and\n            <jats:italic>mexY<\/jats:italic>\n            was also responsive to exposure of cells to tigecycline. To test for the emergence of compensatory efflux pumps in the absence of MexXY-OprM, mutants lacking MexXY-OprM were plated on medium containing tigecycline at 4 or 6 \u03bcg\/ml. Resistant mutants were readily recovered, and these also had decreased susceptibility to several other antibiotics, suggesting efflux pump recruitment. One representative carbenicillin-resistant strain overexpressed OprM, the outer membrane channel component of the MexAB-OprM efflux pump. The\n            <jats:italic>mexAB-oprM<\/jats:italic>\n            repressor gene,\n            <jats:italic>mexR<\/jats:italic>\n            , from this strain contained a 15-bp in-frame deletion. Two representative chloramphenicol-resistant strains showed expression of an outer membrane protein slightly larger than OprM. The\n            <jats:italic>mexCD-OprJ<\/jats:italic>\n            repressor gene,\n            <jats:italic>nfxB<\/jats:italic>\n            , from these mutants contained a 327-bp in-frame deletion and an IS element insertion, respectively. Together, these data indicated drug efflux mediated by MexCD-OprJ. The MICs of the narrower-spectrum semisynthetic tetracyclines doxycycline and minocycline increased more substantially than did those of tigecycline and other glycylcyclines against the MexAB-OprM- and MexCD-OprJ-overexpressing mutant strains. This suggests that glycylcyclines, although they are subject to efflux from\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            , are generally inferior substrates for\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            efflux pumps than are narrower-spectrum tetracyclines.\n          <\/jats:p>","DOI":"10.1128\/aac.47.3.972-978.2003","type":"journal-article","created":{"date-parts":[[2003,2,25]],"date-time":"2003-02-25T18:22:21Z","timestamp":1046197341000},"page":"972-978","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":246,"title":["Efflux-Mediated Resistance to Tigecycline (GAR-936) in\n            <i>Pseudomonas aeruginosa<\/i>\n            PAO1"],"prefix":"10.1128","volume":"47","author":[{"given":"Charles R.","family":"Dean","sequence":"first","affiliation":[{"name":"Wyeth Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Visalli","sequence":"additional","affiliation":[{"name":"Wyeth Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Projan","sequence":"additional","affiliation":[{"name":"Wyeth Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaik-Eng","family":"Sum","sequence":"additional","affiliation":[{"name":"Wyeth Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Bradford","sequence":"additional","affiliation":[{"name":"Wyeth Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2624"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10631.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.428-432.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.14.4275-4284.1999"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.2.317-324.1993"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.19.5803-5805.1996"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.790"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01872-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35023203"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020005"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000417596","volume":"42","year":"1989","unstructured":"Hoiby, N., S. 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