{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T18:59:53Z","timestamp":1774637993102,"version":"3.50.1"},"reference-count":78,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141001"],"award-info":[{"award-number":["32141001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172310"],"award-info":[{"award-number":["82172310"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PKU2025PKULCXQ004"],"award-info":[{"award-number":["PKU2025PKULCXQ004"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    Understanding how bacteria rapidly adapt to recently introduced antibiotics increasingly demands experimental models that move beyond classical evolution systems. We developed a microbial evolution hanging-droplet system (MEHS) that uses gravity-driven flow to sustain continuous exponential growth, doubling daily reproduction rate. Using this MEHS,\n                    <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                    rapidly adapted to fluctuating cefiderocol (CFDC) exposure. However, resistant clones comprised only a minor fraction of the evolved populations. Many mutations overlapped with variants previously observed in clinical practice, including alterations in EnvZ\/OmpR two-component system that reprogrammed siderophore biosynthesis. These changes promoted cross-protection of susceptible subpopulations, alleviating the fitness costs typically associated with resistance and facilitating population-level adaptation. Moreover, the detection of similar variants in clinical isolates collected before CFDC use highlights their latent potential to evolve under selective pressure. Our findings establish MEHS as a powerful platform for resolving clinically relevant resistance trajectories and point to regulatory nodes as potential targets for disrupting cooperative behaviors that undermine antibiotic efficacy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea4527","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T18:00:37Z","timestamp":1774634437000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["EnvZ\/OmpR-driven cooperative behavior promotes cefiderocol resistance in a hanging-droplet evolution system"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2558-1688","authenticated-orcid":true,"given":"Bowen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital, Beijing 100044, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8021-5945","authenticated-orcid":true,"given":"Kaiwen","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital, Beijing 100044, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0269-8435","authenticated-orcid":true,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital, Beijing 100044, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Integrated Circuits, Peking University, Beijing 100871, The People\u2019s Republic of China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-7271","authenticated-orcid":true,"given":"Ruobing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital, Beijing 100044, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-2173","authenticated-orcid":true,"given":"Shitao","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Integrated Circuits, Peking University, Beijing 100871, The People\u2019s Republic of China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5257-7675","authenticated-orcid":true,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Integrated Circuits, Peking University, Beijing 100871, The People\u2019s Republic of China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-0357","authenticated-orcid":true,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital, Beijing 100044, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-025-01169-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00810-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07530-w"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2024.08.014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1909"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-conmatphys-042924-110923"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanmic.2024.101069"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01041-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adr2756"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add1417"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c04482"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag0822"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117716109"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208747"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adv4558"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202306974"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1212449"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01019-24"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01192-20"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.102005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03115-16"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41378-024-00788-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5250"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2015.05.012"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5LC01353D"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05281-4"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-025-03147-1"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-1055-2"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01883-22"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.101034"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13469"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01321"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005872200"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv049"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00059"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00055-X"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13181549"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.91362"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.08.006"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaf048"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071781"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14090893"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-024-00762-y"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00409-06"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12040785"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.43.2200795"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2021.0095"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab888"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2507874122"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2023.127374"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105686"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01601-4"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06193-7"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0284-4"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1659-1668.1997"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0277946"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.02596-14"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213344109"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101083"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu153"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0554-6_12"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad359"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae268"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.12"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_70_2","unstructured":"Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing CLSI Supplement M100 (Clinical and Laboratory Standards Institute Wayne PA ed. 33 2023)."},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2019.03.003"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-017-1008-y"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7837-3_4"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01506-23"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202007166"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129865"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1034"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.13403"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aea4527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T18:01:46Z","timestamp":1774634506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aea4527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":78,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,3,27]]}},"alternative-id":["10.1126\/sciadv.aea4527"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aea4527","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]},"assertion":[{"value":"2025-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaea4527"}}