{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:34:34Z","timestamp":1789198474122,"version":"build-2803163510"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"A. Menarini GmbH"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is important to assess their clinical applicability and potentially prevent resistance development. We compared the laboratory resistance evolution of\n            <jats:italic>Escherichia coli<\/jats:italic>\n            to delafloxacin (DLX) compared to ciprofloxacin (CIP), the co-resistance evolution, and underlying resistance mechanisms at different pHs. Three clones from each of the eight clinical\n            <jats:italic>E. coli<\/jats:italic>\n            isolates were subjected to subinhibitory concentrations of DLX or CIP in parallel at either pH 7.3 or 6.0. Minimum inhibitory concentrations (MICs) were regularly tested (at respective pHs), and the antibiotic concentration was adjusted accordingly. After 30 passages, MICs were determined in the presence of the efflux pump inhibitor phenylalanine-arginine-\u03b2-naphthylamide. Whole genome sequencing of the parental isolates and their resistant derivatives (\n            <jats:italic>n<\/jats:italic>\n            = 54) was performed. Complementation assays were carried out for selected mutations. Quantitative PCR and efflux experiments were carried out for selected derivatives. For DLX-challenged strains, resistance to DLX evolved much slower in acidic than in neutral pH, whereas for CIP-challenged strains, the opposite was the case. Mutations in the quinolone resistance-determining region were mainly seen in CIP-challenged\n            <jats:italic>E. coli<\/jats:italic>\n            , whereas a multifactorial mechanism including mutations in efflux-related genes played a role in DLX resistance evolution (predominantly at pH 6.0). This work provides novel insights into the resistance mechanisms of\n            <jats:italic>E. coli<\/jats:italic>\n            to delafloxacin and highlights the importance of understanding micro-environmental conditions at the infection site that might affect the true clinical efficacy of antibiotics and challenges our current antibiotic susceptibility-testing paradigm.\n          <\/jats:p>","DOI":"10.1128\/aac.01625-22","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:00:33Z","timestamp":1698325233000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Resistance development in\n            <i>Escherichia coli<\/i>\n            to delafloxacin at pHs 6.0 and 7.3 compared to ciprofloxacin"],"prefix":"10.1128","volume":"67","author":[{"given":"Anja","family":"B\u00f6sch","sequence":"first","affiliation":[{"name":"Medical Research Center, Kantonsspital St. Gallen , St. Gallen, Switzerland"},{"name":"Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen , St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magreth E.","family":"Macha","sequence":"additional","affiliation":[{"name":"Medical Research Center, Kantonsspital St. Gallen , St. Gallen, Switzerland"},{"name":"St. Francis University College of Health and Allied Sciences , Morogoro, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-761X","authenticated-orcid":true,"given":"Qun","family":"Ren","sequence":"additional","affiliation":[{"name":"Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology , St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-8934","authenticated-orcid":true,"given":"Philipp","family":"Kohler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen , St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Qi","sequence":"additional","affiliation":[{"name":"Functional Genomics Center Zurich, University of Zurich, ETH Zurich , Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-5882","authenticated-orcid":true,"given":"Baharak","family":"Babouee Flury","sequence":"additional","affiliation":[{"name":"Medical Research Center, Kantonsspital St. Gallen , St. Gallen, Switzerland"},{"name":"Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen , St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.39"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01201-10"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy1079"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4lc00217b"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.05.027"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.01.094"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201801323"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201904007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02509"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-022-00272-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000094668"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9610(05)80576-8"},{"key":"e_1_3_3_14_2","first-page":"1130","article-title":"Role of laparoscopy in the management of acute appendicitis","volume":"124","author":"Heinzelmann M","year":"1999","unstructured":"Heinzelmann M , Sch\u00f6b O , Gianom D , Platz A , Simmen HP . 1999. Role of laparoscopy in the management of acute appendicitis. Zentralbl Chir 124:1130\u20131136.","journal-title":"Zentralbl Chir"},{"key":"e_1_3_3_15_2","first-page":"313","volume-title":"New dimensions fo antimicrobial therapy","author":"Bryant RE","year":"1984","unstructured":"Bryant RE . 1984. Effect of the suppurative environment on antibiotic activity, p 313\u2013357. In Root RK , MA Sande (ed), New dimensions fo antimicrobial therapy. , Churchill Livingstone, New York."},{"key":"e_1_3_3_16_2","unstructured":"2020. EUCAST: AST of Bacteria. Available from: https:\/\/www.eucast.org\/ast_of_bacteria. Retrieved 24 Jun 2020."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl489"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz434"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802609789630947"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01049-15"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv449"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.9.2328-2334.1995"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00043-12"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2018-0067"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1028560"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02792-18"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.20.5803-5812.2001"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.1126-1136.2001"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab421"},{"key":"e_1_3_3_30_2","first-page":"319","article-title":"Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria","volume":"3","author":"Rodionov DA","year":"2001","unstructured":"Rodionov DA , Gelfand MS , Mironov AA , Rakhmaninova AB . 2001. Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria. J Mol Microbiol Biotechnol 3:319\u2013324.","journal-title":"J Mol Microbiol Biotechnol"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01930-10"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00997.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1865-1868.2000"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00281-21"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01448-09"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl426"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025320"},{"key":"e_1_3_3_38_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u2014ninth edition","author":"CLSI M07-A9","year":"2012","unstructured":"CLSI M07-A9 . 2012 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u2014ninth edition"},{"key":"e_1_3_3_39_2","volume-title":"Methods for determining bactericidal activity of antimicrobial agents; approved guideline","author":"CLSI M26-A","year":"1999","unstructured":"CLSI M26-A . 1999. Methods for determining bactericidal activity of antimicrobial agents; approved guideline. Vol. 19. 18 vols."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology11010046"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24030470"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060666"},{"key":"e_1_3_3_43_2","unstructured":"Andrews S Krueger F Segonds-Pichon A Biggins L Krueger C Wingett S\n. 2010. FastQC: a quality control tool for high throughput sequence data. Available from: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15931.2"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-12-18"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.12.015"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00840-16"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01625-22","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01625-22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T14:08:52Z","timestamp":1700057332000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01625-22"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11,15]]}},"alternative-id":["10.1128\/aac.01625-22"],"URL":"https:\/\/doi.org\/10.1128\/aac.01625-22","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]},"assertion":[{"value":"2022-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01625-22"}}