Cefiderocol resistance genes identified in environmental samples using functional metagenomics
Artikel i vetenskaplig tidskrift, 2026
Antibiotic resistance poses a global public health threat, which can originate from the transfer of environmental antibiotic resistance genes to pathogenic bacteria, as highlighted by the "One Health" framework. Cefiderocol is a siderophore cephalosporin recently introduced in clinical practice which displays a "Trojan Horse" mechanism, utilizing bacterial iron transportation systems for cell entry. Although it is only used as a last-line antibiotic, resistance has already been observed in clinical isolates. Yet, cefiderocol resistance genes are difficult to monitor as resistance mechanisms remain mostly undescribed in antibiotic resistance gene databases and therefore uncharacterized in the environment. To address this critical gap, we applied functional metagenomics to diverse environmental samples (wastewater, freshwater, and soil) from France, Germany, Sweden, and Pakistan. Four antibiotic resistant genes were identified as responsible for increased cefiderocol minimum inhibitory concentrations to clinically-relevant levels (ranging from 1 to 4 mg/l), including ꞵ-lactamases (VEB-3, OXA-372 homolog, and YbxI homolog) and a partial penicillin-binding protein homolog. None of these genes had been previously reported as a cefiderocol resistance gene. Three out of four had their closest homologs in pathogenic bacteria. The blaVEB-3 gene was associated with a mobile genetic element and distributed across all wastewater metagenomes analyzed in this study. We therefore highlight the critical need for functional metagenomics, to characterize previously uncharacterized last-line antibiotic resistance mechanisms which will be used to enrich antibiotic resistance gene databases and thereby improving antibiotic resistance surveillance in all One Health compartments.
antibiotic resistance
cefiderocol
functional metagenomics
Författare
Rémi Gschwind
Université Paris Descartes
Mehdi Bonnet
Hôpital Beaujon
Université Paris Descartes
Anna Abramova
Göteborgs universitet
Chalmers, Life sciences, Systembiologi
Víctor Hugo Jarquín-Díaz
Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.
Charité Universitätsmedizin Berlin
Helmholtz-Gemeinschaft Deutscher Forschungszentren
Marcus Wenne
Göteborgs universitet
Chalmers, Life sciences, Systembiologi
Ulrike Löber
Charité Universitätsmedizin Berlin
Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.
Helmholtz-Gemeinschaft Deutscher Forschungszentren
Nicolas Godron
Université Paris Descartes
Ioannis D. Kampouris
Technische Universität Dresden
Faina Tskhay
Technische Universität Dresden
Fouzia Nahid
Quaid-i-Azam University
Chloé Debroucker
Université Paris Descartes
Maximilien Bui-Hai
Université Paris Descartes
Inès El Aiba
Université Paris Descartes
Uli Klümper
Technische Universität Dresden
Thomas U. Berendonk
Technische Universität Dresden
Sofia K. Forslund
Deutsches Zentrum für Herz-Kreislauf-Forschung e. V.
Structural and Computational Biology Unit
Helmholtz-Gemeinschaft Deutscher Forschungszentren
Charité Universitätsmedizin Berlin
Rabaab Zahra
Quaid-i-Azam University
Johan Bengtsson Palme
Göteborgs universitet
Chalmers, Life sciences, Systembiologi
Etienne Ruppé
Hôpital Bichat-Claude-Bernard AP-HP
Université Paris Descartes
ISME Journal
1751-7362 (ISSN) 1751-7370 (eISSN)
Vol. 20 1 wrag010Framtidens patogener och resistensgener
Stiftelsen för Strategisk forskning (SSF) (FFL21-0174), 2022-08-01 -- 2027-12-31.
Etablering av normalnivåer för antibiotikaresistens i olika miljöer för miljöövervakning
Vetenskapsrådet (VR) (2019-00299), 2022-05-01 -- 2023-12-31.
Övervakning av framtidens antibiotikaresistens genom karaktärisering av nya resistensgener i miljön
Vetenskapsrådet (VR) (2023-01721), 2023-12-01 -- 2026-11-30.
Ämneskategorier (SSIF 2025)
Infektionsmedicin
Mikrobiologi inom det medicinska området
Mikrobiologi
DOI
10.1093/ismejo/wrag010
PubMed
41603547
Relaterade dataset
RemiGSC/Mgf_FDC: Cefiderocol resistance studied using Functional metagenomics [dataset]
URI: https://zenodo.org/records/15487633