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program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to analyse the interplay between impaired iron uptake and \u03b2-lactamases on cefiderocol resistance in Pseudomonas aeruginosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-one transferable \u03b2-lactamases and 16 intrinsic P. aeruginosa AmpC (PDC) variants were cloned and expressed in wild-type (PAO1) and iron uptake-deficient (PAO \u0394piuC) P. aeruginosa backgrounds. MICs of cefiderocol and antipseudomonal \u03b2-lactams were determined by reference broth microdilution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Relative to PAO1, deletion of piuC caused a specific 16-fold decrease in cefiderocol activity but negligible effects on the activity of other \u03b2-lactams. Among transferable \u03b2-lactamases, SHV-12, KPC \u03a9-loop mutants, NDMs and OXA-15 showed cefiderocol MIC values above the clinical breakpoint (2\u2005mg\/L) when expressed in PAO1. When expressed in PAO \u0394piuC, these and the transformants harbouring PER-1, VEB-1, KPC-2, KPC-3, VIM-1, CMY-2, OXA-2 and OXA-14 showed increased MIC values from 16 to &amp;gt;256\u2005mg\/L. The PDC variants carrying the \u03a9-loop changes \u0394P215-G222 (PDC-577), E219K (PDC-221 and PDC-558) and the H10 helix change L293P (PDC-219) had the greatest impact on cefiderocol resistance, with MICs of 2\u20134\u2005mg\/L in PAO1 and of up to 32\u201364\u2005mg\/L in PAO \u0394piuC. Widespread enzymes such as GES, CTX-M-9, CTX-M-15, VIM-2-like enzymes, IMPs, DHA-1, FOX-4, OXA-10, OXA-48 and the other PDC variants tested had weaker effects on cefiderocol resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We add evidence about the effect of the interplay between iron uptake and \u03b2-lactamases on the acquisition of cefiderocol resistance in P. aeruginosa. These findings may help to anticipate the emergence of resistance and optimize the use of cefiderocol against P. aeruginosa infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae326","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T11:50:33Z","timestamp":1725277833000},"page":"3023-3028","source":"Crossref","is-referenced-by-count":22,"title":["Impact of transferable \u03b2-lactamases and intrinsic AmpC amino acid substitutions on the activity of cefiderocol against wild-type and iron uptake-deficient mutants of\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-3784","authenticated-orcid":false,"given":"Luc\u00eda","family":"Gonz\u00e1lez-Pinto","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario A 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