Cited by 357Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyAntibiotics Pharmacokinetics and Efficacy

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Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa

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Ito, Akinobu, Nishikawa, Toru, Matsumoto, Shuhei, Yoshizawa, Hidenori, Sato, Takafumi, Nakamura, Rio, Tsuji, Masakatsu, Yamano, Yoshinori·2016·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01405-16PMC PMC5119021

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Abstract

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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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
ORCID: Matsumoto, Shuhei
Yoshizawa, Hidenori
Sato, Takafumi
Nakamura, Rio
Yamano, Yoshinori
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
DOI: 10.1128/aac.01405-16
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
journals.asm.org/non-commercial-tdm-license (tdm)
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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Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa

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