{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:04:06Z","timestamp":1787843046276,"version":"build-2784847793"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"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":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The resistance mechanism of Gram-negative bacteria to the siderophore antibiotic cefiderocol is primarily attributed to carbapenemase and siderophore uptake pathways; however, specific factors and their relationships remain to be fully elucidated. Here, we constructed cefiderocol-resistant\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              (CRKP) strains carrying different carbapenemases and knocked out siderophore genes to investigate the roles of various carbapenemases and siderophores in the development of cefiderocol resistance. Antimicrobial susceptibility testing revealed that both\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>NDM<\/jats:sub>\n              and\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>KPC<\/jats:sub>\n              significantly increased the minimum inhibitory concentration (MIC) of\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              (KP) to cefiderocol, while\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>OXA-48<\/jats:sub>\n              showed a modest increase. Notably, KP expressing NDM exhibited a higher cefiderocol MIC compared to KP expressing KPC, although expression of NDM alone did not induce cefiderocol resistance. Laboratory evolutionary experiments demonstrated that combining pNDM with mutations in the siderophore uptake receptor gene\n              <jats:italic>cirA<\/jats:italic>\n              and pKPC with a mutation in the two-component system gene\n              <jats:italic>envZ<\/jats:italic>\n              led to KP reaching a high level of cefiderocol resistance. Although combining pOXA with mutations in the two-component system gene\n              <jats:italic>baeS<\/jats:italic>\n              did not induce cefiderocol resistance, it significantly reduced susceptibility. Moreover, siderophores could influence the development of cefiderocol resistance. Strains deficient in enterobactin exhibited increased susceptibility to cefiderocol, while deficiencies in yersiniabactin and salmochelin showed no significant alterations. In conclusion, carbapenemase gene expression facilitates cefiderocol resistance, but its presence alone is insufficient. Cefiderocol resistance in CRKP typically involves abnormal expression of certain genes and other factors, such as mutations in siderophore uptake receptor genes and two-component system genes. The enterobactin siderophore synthesis gene\n              <jats:italic>entB<\/jats:italic>\n              may also contribute to resistance.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01019-24","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T13:00:38Z","timestamp":1730206838000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Effects of different carbapenemase and siderophore production on cefiderocol susceptibility in\n            <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"68","author":[{"given":"Chengcheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6020-4107","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"MOE Key Laboratory of Geriatric Diseases and Immunology, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Key Laboratory of Alkene-Carbon Fibres-Based Technology and Application for Detection of Major Infectious Diseases","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicheng","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feinan","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxiang","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-1523","authenticated-orcid":true,"given":"Hong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"MOE Key Laboratory of Geriatric Diseases and Immunology, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Key Laboratory of Alkene-Carbon Fibres-Based Technology and Application for Detection of Major Infectious Diseases","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc6821"},{"key":"e_1_3_2_5_2","first-page":"165","article-title":"Vital signs: carbapenem-resistant Enterobacteriaceae","volume":"62","author":"Centers for Disease Control and Prevention (CDC)","year":"2013","unstructured":"Centers for Disease Control and Prevention (CDC). 2013. Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep 62:165\u2013170.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix646"},{"key":"e_1_3_2_7_2","unstructured":"WHO updates list of drug-resistant bacteria most threatening to human health. 2024 Available from: https:\/\/www.who.int\/news\/item\/17-05-2024-who-updates-list-of-drug-resistant-bacteria-most-threatening-to-human-health"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz826"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01580-4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-1055-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.10.007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.101034"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab511"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.01779-21"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00877-21"},{"key":"e_1_3_2_16_2","unstructured":"AST news update June 2023: the latest on testing cefiderocol. 2023 Clinical & Laboratory Standards Institute. Available from: https:\/\/clsi.org\/about\/blog\/ast-news-update-june-2023-the-latest-on-testing-cefiderocol"},{"key":"e_1_3_2_17_2","unstructured":"Eucast: clinical breakpoints and dosing of antibiotics. 2023. Available from: https:\/\/www.eucast.org\/clinical_breakpoints"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01192-20"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00358-23"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01291-22"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2022.2128764"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2020.07.009"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2022.106646"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01454-17"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2021.01.021"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00012-07"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0630018100"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1924019"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.04.008"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-19"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01582-20"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa117"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01801-18"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00213-21"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2019.03.003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6792"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02171-20"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01834-18"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01019-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01019-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T14:04:28Z","timestamp":1733407468000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01019-24"}},"subtitle":[],"editor":[{"given":"Alessandra","family":"Carattoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12,5]]}},"alternative-id":["10.1128\/aac.01019-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01019-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]},"assertion":[{"value":"2024-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01019-24"}}