{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T02:35:23Z","timestamp":1774924523197,"version":"3.50.1"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The effect of a meropenem-ciprofloxacin combination (MCC) on the susceptibility of multidrug-resistant (MDR)\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            (MRPA) clinical isolates was determined using checkerboard and time-kill curve techniques. Structural changes and differential gene expression that resulted from the synergistic action of the MCC against one of the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            isolates (1071-MRPA]) were evaluated using electron microscopy and representational difference analysis (RDA), respectively. The differentially expressed, SOS response-associated, and resistance-associated genes in 1071-MRPA exposed to meropenem, ciprofloxacin, and the MCC were monitored by quantitative PCR. The MCC was synergistic against 25% and 40.6% of MDR\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            isolates as shown by the checkerboard and time-kill curves, respectively. The morphological and structural changes that resulted from the synergistic action of the MCC against 1071-MRPA were a summation of the effects observed with each antimicrobial alone. One exception included outer membrane vesicles, which were seen in a greater amount upon ciprofloxacin exposure but were significantly inhibited upon MCC exposure. Cell wall- and DNA repair-associated genes were differentially expressed in 1071-MRPA exposed to meropenem, ciprofloxacin, and the MCC. However, some of the RDA-detected, resistance-associated, and SOS response-associated genes were expressed at significantly lower levels in 1071-MRPA exposed to the MCC. The MCC may be an alternative for the treatment of MDR\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            . The effect of this antimicrobial combination may be not only the result of a summation of the effects of meropenem and ciprofloxacin but also a result of differential action that likely inhibits protective mechanisms in the bacteria.\n          <\/jats:p>","DOI":"10.1128\/aac.02584-13","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T03:36:16Z","timestamp":1399347376000},"page":"3957-3967","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Structural Changes and Differentially Expressed Genes in Pseudomonas aeruginosa Exposed to Meropenem-Ciprofloxacin Combination"],"prefix":"10.1128","volume":"58","author":[{"given":"Vera L\u00facia Dias","family":"Siqueira","sequence":"first","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"},{"name":"Department of Clinical Analysis and Biomedicine, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosilene Fressatti","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Biomedicine, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katiany Rizzieri","family":"Caleffi-Ferracioli","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Biomedicine, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regiane Bertin","family":"de Lima Scodro","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Biomedicine, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Aparecida","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Genetics, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Fiorini","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Biomedicine, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Ueda-Nakamura","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedito Prado","family":"Dias-Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celso Vataru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, State University of Maringa, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.11.168"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.009142-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2006.03.014"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00796-07"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01681.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp201"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01576-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.02.019"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028177"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00065-10"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl063"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365540110027222"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2004.11.005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00689-07"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000074529"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir120"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.09.108"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1984-82502013000100006"},{"key":"e_1_3_2_20_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; 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