{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T06:01:57Z","timestamp":1780293717871,"version":"3.54.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100023448","name":"Robert Koch Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023448","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Ministry of Health","award":["1369-402"],"award-info":[{"award-number":["1369-402"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the emergence of resistance to cefiderocol (FDC) in clinical Enterobacter hormaechei isolates and to elucidate the underlying genetic mechanisms, with particular focus on mutations in a putative TonB-dependent receptor (TBDR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five non-duplicate clinical FDC-susceptible E. hormaechei isolates were exposed to stepwise increasing concentrations of FDC using disk diffusion and broth microdilution to select for spontaneous FDC-resistant mutants. WGS was performed to identify resistance-associated mutations. Site-directed mutagenesis via CRISPR-Cas9 was employed to confirm causality. Bacterial fitness was evaluated by growth curve experiments under both standard and iron-depleted conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six spontaneous mutants exhibited increased FDC MICs ranging from 2 to 16\u2005mg\/L. All mutants carried distinct mutations in the TBDR gene, including frameshift mutations and premature stop codons. CRISPR-engineered strains harbouring identical mutations displayed the same resistance phenotype, confirming that disruption of TBDR is sufficient to confer increased FDC resistance. Susceptibility to other \u03b2-lactams remained unaffected. Growth analyses did not reveal an obvious growth defect in TBDR mutants compared to the parental strain under the tested in vitro conditions, including iron-depleted media.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies mutations in a putative TBDR as a key mechanism mediating FDC resistance in E. hormaechei. The absence of an obvious growth defect under the tested in vitro conditions suggests that loss of this receptor does not impose a major growth disadvantage. These findings underscore the role of TBDRs in FDC uptake and highlight the potential for resistance development under antibiotic selection pressure through disruption of siderophore-mediated uptake pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag193","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:42:04Z","timestamp":1779363724000},"source":"Crossref","is-referenced-by-count":0,"title":["Influence of a putative TonB-dependent receptor on cefiderocol susceptibility in clinical\n                    <i>Enterobacter hormaechei<\/i>\n                    isolates"],"prefix":"10.1093","volume":"81","author":[{"given":"Pia","family":"Turowski","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, German National Reference Centre for Multidrug-Resistant Gram-Negative Bacteria, Ruhr-University Bochum , Bochum 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