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Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa
Open accessAbstract
Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the third-position side chain. The in vitro activity of cefiderocol against Pseudomonas aeruginosa was enhanced under iron-depleted conditions, whereas that of ceftazidime was not affected. The monitoring of [thiazole- 14 C]cefiderocol revealed the increased intracellular accumulation of cefiderocol in P. aeruginosa cells incubated under iron-depleted conditions compared with those incubated under iron-sufficient conditions. Cefiderocol was shown to have potent chelating activity with ferric iron, and extracellular iron was efficiently transported into P. aeruginosa cells in the presence of cefiderocol as well as siderophores, while enhanced transport of extracellular ferric iron was not observed when one of the hydroxyl groups of the catechol moiety of cefiderocol was replaced with a methoxy group. We conclude that cefiderocol forms a chelating complex with iron, which is actively transported into P. aeruginosa cells via iron transporters, resulting in potent antibacterial activity of cefiderocol against P. aeruginosa .
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“Apart from binding their primary ligand, FeEnt, with high affinity, and its aposiderophore Ent with 100-200-fold lower affinity (38), KpnFepA_1658, KpnIroN, and KpnFepA_4984 showed different preferences for ferric catecholate complexes and siderophore antibiotics cefiderocol [FeFDC (40,41)] and FeMB-1 (42,43):”
From Siderophore-mediated iron acquisition by Klebsiella pneumoniae (2024) · cites this paper as [40]
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Metadata
- Authors
- Ito, A., Nishikawa, T., Matsumoto, S., Yoshizawa, H., Sato, T., Nakamura, R., Tsuji, M., & Yamano, Y.
- Affiliations
- Shionogi (Japan) (JP)
- Corresponding author
- Ito, Akinobu
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2016-12
- Volume
- 60
- Issue
- 12
- Pages
- 7396-7401
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5119021
- OpenAlex
- W2530661320
- Cited by
- 352
- References
- 33
- Citations by year
- 2026: 52 · 2025: 34 · 2024: 35 · 2023: 37 · 2022: 40 · 2021: 37 · 2020: 41 · 2019: 29 · 2018: 30 · 2017: 16 · 2016: 1
- FWCI
- 12.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- cefiderocol, siderophore cephalosporin, Pseudomonas aeruginosa, iron chelation, catechol moiety, iron depletion, intracellular accumulation, iron transporters, antibacterial activity, ceftazidime
- MeSH terms
- Cefiderocol, Anti-Bacterial Agents, Biological Transport, Carbon Radioisotopes, Ceftazidime, Cephalosporins, Fluoresceins, Fluorescent Dyes, Iron, Iron Chelating Agents, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Structure-Activity Relationship, Thiazoles
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