{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:56:01Z","timestamp":1792281361365,"version":"4.4.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["PID2021-127402OB-I00, CEX2018-000806-S"],"award-info":[{"award-number":["PID2021-127402OB-I00, CEX2018-000806-S"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Government of Catalonia | Departament d'Universitats, Recerca i Societat de la Informaci\u00f3","award":["2017 SGR 0809"],"award-info":[{"award-number":["2017 SGR 0809"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"crossref","award":["CERCA"],"award-info":[{"award-number":["CERCA"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015268","name":"Ministerio de Sanidad, Consumo y Bienestar","doi-asserted-by":"crossref","award":["CM23\/00277"],"award-info":[{"award-number":["CM23\/00277"]}],"id":[{"id":"10.13039\/501100015268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100023561","name":"Ministerio de Universidades","doi-asserted-by":"crossref","award":["Margarita Salas"],"award-info":[{"award-number":["Margarita Salas"]}],"id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              is an opportunistic pathogen capable of causing severe infections in immunocompromised individuals, who often require prolonged antibiotic therapy. The emergence of carbapenemase-producing\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              has further complicated the management of nosocomial infections, limiting therapeutic options. Cefiderocol has recently emerged as a promising antipseudomonal agent, using the bacterial iron transport system to gain entry into the cell; however, there have been reports of\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              resistant to cefiderocol. We describe the\n              <jats:italic>in vivo<\/jats:italic>\n              cefiderocol resistance progression of four consecutive\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              isolates from one patient with T-cell acute lymphoblastic leukemia. Analysis of potential genes involved in cefiderocol transport resulted in three genes mutated in two resistant isolates. One isolate presented a S116F substitution in PiuC, and the other presented a deletion of 29 amino acids in the signal peptide of PiuA and a STOP substitution in PirA, resulting in the deletion of a piece of the channel. These mutations increased 24- and 64-folds the cefiderocol minimum inhibitory concentration, respectively. The mutations in the aforementioned genes may directly impact siderophore internalization, thereby contributing to an elevation in the MIC of the antibiotic.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Carbapenem-resistant\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              poses a significant challenge due to its broad antibiotic resistance. Cefiderocol is a novel antibiotic aimed at combating infections caused by such organisms. However, if these pathogens develop resistance to this new drug, it hinders treatment efficacy and options. Therefore, it is crucial to identify and describe mutations in the genes involved in the uptake of cefiderocol to find better treatment strategies for patients infected with multidrug-resistant\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01928-24","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T14:00:36Z","timestamp":1738072836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Novel PiuC, PirA, and PiuA mutations leading to\n            <i>in vivo<\/i>\n            cefiderocol resistance progression in IMP-16- and KPC-2-producing\n            <i>Pseudomonas aeruginosa<\/i>\n            from a leukemic patient"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-5236","authenticated-orcid":true,"given":"Joaquim","family":"Vi\u00f1es","sequence":"first","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Servei Veterinari de Gen\u00e8tica Molecular (SVGM), Facultat de Veterin\u00e0ria, Universitat Aut\u00f2noma de Barcelona","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5046-4490","authenticated-orcid":true,"given":"Andrea","family":"Vergara","sequence":"additional","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-1576","authenticated-orcid":true,"given":"Ignasi","family":"Roca","sequence":"additional","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8025-3926","authenticated-orcid":true,"given":"Jordi","family":"Vila","sequence":"additional","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-6318","authenticated-orcid":true,"given":"Tommaso Francesco","family":"Aiello","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"del R\u00edo","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lopera","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Garcia-Vidal","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Climent","family":"Casals-Pascual","sequence":"additional","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c0lex","family":"Soriano","sequence":"additional","affiliation":[{"name":"Departament de Malalties Infeccioses, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]},{"name":"CIBER Enfermedades Infecciosas (CIBERINFEC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pitart","sequence":"additional","affiliation":[{"name":"Servei de Microbiologia i Parasitologia-CDB, Hospital Cl\u00ednic de Barcelona","place":["Barcelona, Spain"]},{"name":"Institut de Salut Global (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Departament de Fonaments Cl\u00ednics, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"ECDC. 2020. Antimicrobial resistance in the EU\/EEA (EARS-Net) - Annual Epidemiological Report 2019. Stockholm."},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab295"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy378"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00614-24"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae126"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03836-23"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"e_1_3_5_10_2","unstructured":"Oxford Nanopore Technologies. 2018. Medaka. GitHub."},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.186072.114"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv351"},{"key":"e_1_3_5_13_2","unstructured":"Seemann T. 2017. Abricate. GitHub."},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1004"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02412-14"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.14826.1"},{"key":"e_1_3_5_17_2","first-page":"95","article-title":"BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall TA","year":"1999","unstructured":"Hall TA. 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT. Nucleic Acids Symp Ser 41:95\u201398.","journal-title":"Nucleic Acids Symp Ser"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_3_5_20_2","unstructured":"Oxoglutarate\/iron-dependent dioxygenase (IPR005123) - InterPro entry. InterPro"},{"key":"e_1_3_5_21_2","unstructured":"piuC - PKHD-type hydroxylase PiuC - Pseudomonas aeruginosa (strain ATCC 15692 \/ DSM 22644 \/ CIP 104116 \/ JCM 14847 \/ LMG 12228 \/ 1C \/ PRS 101 \/ PAO1). UniProtKB | UniProt"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad172"},{"key":"e_1_3_5_23_2","unstructured":"piuA - Hydroxamate-type ferrisiderophore receptor - Pseudomonas aeruginosa. UniProtKB | UniProt"},{"key":"e_1_3_5_24_2","unstructured":"pirA - Ferric enterobactin receptor PirA - Pseudomonas aeruginosa (strain ATCC 15692 \/ DSM 22644 \/ CIP 104116 \/ JCM 14847 \/ LMG 12228 \/ 1C \/ PRS 101 \/ PAO1). UniProtKB | UniProt"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/life13071427"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11060723"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11050579"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab888"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa439.1450"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00097-18"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01454-17"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlaa081"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2021.12.017"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.11.014"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab311"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1909"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-022-04526-0"},{"key":"e_1_3_5_38_2","first-page":"37","volume-title":"Current topics in membranes","author":"Schalk IJ","year":"2012","unstructured":"Schalk IJ, Mislin GLA, Brillet K. 2012. Structure, function and binding selectivity and stereoselectivity of siderophore\u2013iron outer membrane transporters, p 37\u201366. In Current topics in membranes"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02531-16"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05021"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.63.1.161-173.1999"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02474-12"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00831-15"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.07.030"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01345-12"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01928-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01928-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T14:10:50Z","timestamp":1741097450000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01928-24"}},"subtitle":[],"editor":[{"given":"Felix Ngosa","family":"Toka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,4]]}},"alternative-id":["10.1128\/spectrum.01928-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01928-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"2024-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01928-24"}}