Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa
Open Access
- 1 December 2016
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 60 (12), 7396-7401
- https://doi.org/10.1128/aac.01405-16
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-14C]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.Keywords
This publication has 32 references indexed in Scilit:
- Involvement of Fe Uptake Systems and AmpC β-Lactamase in Susceptibility to the Siderophore Monosulfactam BAL30072 in Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2013
- “Stormy waters ahead”: global emergence of carbapenemasesFrontiers in Microbiology, 2013
- Clinically Relevant Gram-Negative Resistance Mechanisms Have No Effect on the Efficacy of MC-1, a Novel Siderophore-Conjugated MonocarbamAntimicrobial Agents and Chemotherapy, 2012
- Current Epidemiology and Growing Resistance of Gram-Negative PathogensThe Korean Journal of Internal Medicine, 2012
- Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistanceFEMS Microbiology Reviews, 2011
- Emergence of NDM-1 Metallo-β-Lactamase in Pseudomonas aeruginosa Clinical Isolates from SerbiaAntimicrobial Agents and Chemotherapy, 2011
- In Vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity against Multiresistant Gram-Negative BacilliAntimicrobial Agents and Chemotherapy, 2010
- Iron uptake regulation in Pseudomonas aeruginosaBioMetals, 2009
- Role of outer membrane protein OprD and penicillin-binding proteins in resistance of Pseudomonas aeruginosa to imipenem and meropenemInternational Journal of Antimicrobial Agents, 2008
- Metallo beta lactamases inPseudomonas aeruginosaand Acinetobacter speciesExpert Opinion on Investigational Drugs, 2008