{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:13:52Z","timestamp":1791422032368,"version":"4.3.3"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"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":[[2019,9]]},"abstract":"<jats:p>Multitargeting antibiotics, i.e., single compounds capable of inhibiting two or more bacterial targets, are generally considered to be a promising therapeutic strategy against resistance evolution. The rationale for this theory is that multitargeting antibiotics demand the simultaneous acquisition of multiple mutations at their respective target genes to achieve significant resistance. The theory presumes that individual mutations provide little or no benefit to the bacterial host.<\/jats:p>","DOI":"10.1128\/aac.00207-19","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T07:58:26Z","timestamp":1561449506000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Rapid Evolution of Reduced Susceptibility against a Balanced Dual-Targeting Antibiotic through Stepping-Stone Mutations"],"prefix":"10.1128","volume":"63","author":[{"given":"Petra","family":"Szili","sequence":"first","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"},{"name":"Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Draskovits","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"R\u00e9v\u00e9sz","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"},{"name":"Doctoral School of Theoretical Medicine, University of Szeged, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Bog\u00e1r","sequence":"additional","affiliation":[{"name":"MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Szeged, Hungary"},{"name":"Department of Medical Chemistry, University of Szeged, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"Balogh","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Martinek","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, University of Szeged, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejla","family":"Daruka","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9ka","family":"Spohn","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint M\u00e1rk","family":"V\u00e1s\u00e1rhelyi","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Czikkely","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"},{"name":"Szeged Scientists Academy, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Kintses","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"},{"name":"Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Gr\u00e9zal","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgyi","family":"Ferenc","sequence":"additional","affiliation":[{"name":"Nucleic Acid Synthesis Laboratory, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"P\u00e1l","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-490X","authenticated-orcid":false,"given":"\u00c1kos","family":"Nyerges","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/420937"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky019"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2015.02.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009940"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2202"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7NP00006E"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/423841"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02047-16"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02778-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084409"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msv243"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm900028n"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04077-14"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy145"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02095-16"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02820-15"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00468-17"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801646115"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30754-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar000033j"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3922"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2011.07.005"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.75"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.05.012"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy074"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2661"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/107662903322286472"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.06.010"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003592"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025320"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-78538-7_16"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1892"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-011-3557-z"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000475"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01221-18"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.11.005"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1796"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0164-0"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag0822"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.03.106"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1252-9"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000541"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12830"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01243-18"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70780-7"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706988"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep11827"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01377"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky022"},{"key":"e_1_3_3_52_2","volume-title":"Small-Molecule Drug Discovery Suite 2017-4","author":"Schr\u00f6dinger, LLC","year":"2017","unstructured":"Schr\u00f6dinger, LLC. 2017. Small-Molecule Drug Discovery Suite 2017-4. Schr\u00f6dinger, LLC, New York, NY."},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00864"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-015-7658-1_21"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1109\/SC.2006.54"},{"key":"e_1_3_3_56_2","volume-title":"Schr\u00f6dinger release 2017-4: Bioluminate","author":"Schr\u00f6dinger, LLC","year":"2017","unstructured":"Schr\u00f6dinger, LLC. 2017. Schr\u00f6dinger release 2017-4: Bioluminate. Schr\u00f6dinger, LLC, New York, NY."},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24694"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.002"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7387"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm060522a"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci300425v"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520040113"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.12846"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2508"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00378"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2000644"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2435976100"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw009"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.es.21.110190.002105"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00752-06"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700721114"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-2836(02)00470-9"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10613"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798316001212"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.17226\/25801"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00207-19","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00207-19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:23:50Z","timestamp":1645460630000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00207-19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":76,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1128\/AAC.00207-19"],"URL":"https:\/\/doi.org\/10.1128\/aac.00207-19","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/495630","asserted-by":"object"}]},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9]]},"assertion":[{"value":"2019-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00207-19"}}