{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:37:03Z","timestamp":1789915023381,"version":"4.0.1"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"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":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            BAL30072 is a monosulfactam conjugated with an iron-chelating dihydroxypyridone moiety. It is active against Gram-negative bacteria, including multidrug-resistant\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            . We selected mutants with decreased susceptibilities to BAL30072 in\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            PAO1 under a variety of conditions. Under iron-deficient conditions, mutants with overexpression of AmpC \u03b2-lactamase predominated. These mutants were cross-resistant to aztreonam and ceftazidime. Similar mutants were obtained after selection at &gt;16\u00d7 the MIC in iron-sufficient conditions. At 4\u00d7 to 8\u00d7 the MIC, mutants with elevated MIC for BAL30072 but unchanged MICs for aztreonam or ciprofloxacin were selected. The expression of\n            <jats:italic>ampC<\/jats:italic>\n            and the major efflux pump genes were also unchanged. These BAL30072-specific mutants were characterized by transcriptome analysis, which revealed upregulation of the Fe-dicitrate operon, FecIRA. Whole-genome sequencing showed that this resulted from a single nucleotide change in the Fur-box of the\n            <jats:italic>fecI<\/jats:italic>\n            promoter. Overexpression of either the FecI ECF sigma factor or the FecA receptor increased BAL30072 MICs 8- to 16-fold. A\n            <jats:italic>fecI<\/jats:italic>\n            mutant and a\n            <jats:italic>fecA<\/jats:italic>\n            mutant of PAO1 were hypersusceptible to BAL30072 (MICs &lt; 0.06 \u03bcg\/ml). The most downregulated gene belonged to the pyochelin synthesis operon, although mutants in pyochelin receptor or synthesis genes had unchanged MICs. The\n            <jats:italic>piuC<\/jats:italic>\n            gene, coding for a Fe(II)-dependent dioxygenase located next to the\n            <jats:italic>piuA<\/jats:italic>\n            iron receptor gene, was also downregulated. The MICs of BAL30072 for\n            <jats:italic>piuC<\/jats:italic>\n            and\n            <jats:italic>piuA<\/jats:italic>\n            transposon mutants were increased 8- and 16-fold, respectively. We conclude that the upregulation of the Fe-dicitrate system impacts the expression of other TonB-dependent iron transporters and that PiuA and PiuC contribute to the susceptibility of\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            PAO1 to BAL30072.\n          <\/jats:p>","DOI":"10.1128\/aac.02474-12","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T06:06:30Z","timestamp":1361340390000},"page":"2095-2102","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Involvement of Fe Uptake Systems and AmpC \u03b2-Lactamase in Susceptibility to the Siderophore Monosulfactam BAL30072 in Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"57","author":[{"given":"Christian","family":"van Delden","sequence":"first","affiliation":[{"name":"Service of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm G. P.","family":"Page","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International, Ltd., Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland"},{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2010.515588"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945008785747734"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.06.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-009-9219-2"},{"key":"e_1_3_3_6_2","first-page":"561","article-title":"New molecules from old classes: revisiting the development of beta-lactams","volume":"12","author":"Page MG","year":"2009","unstructured":"PageMG HeimJ. 2009. New molecules from old classes: revisiting the development of beta-lactams. IDrugs 12:561\u2013565.","journal-title":"IDrugs"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.156.1.308-315.1983"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/b516237h"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.1.104"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(96)00217-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1010"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.4.653"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.03.019"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01525-09"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2009.08.003"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.023531-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.1.235-242.1997"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2010.02372.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.12.007"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.18.5438-5446.1996"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(02)01422-0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.1.45-54.2006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb01991.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2036282100"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.3.1361-1367.1990"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-008-9193-0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000353"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.145.1.156-163.1981"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.381426.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.613"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.159.1.271-277.1984"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.2.754-760.1989"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00830-10"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01345-12"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05366.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00807-06"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3222-3227.2005"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-6-115"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02474-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02474-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T13:50:13Z","timestamp":1645451413000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02474-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1128\/AAC.02474-12"],"URL":"https:\/\/doi.org\/10.1128\/aac.02474-12","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5]]},"assertion":[{"value":"2012-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}