ArticlePloS one2022
Elucidating the effect of iron acquisition systems in Klebsiella pneumoniae on susceptibility to the novel siderophore-cephalosporin cefiderocol.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Influence of iron uptake systems on cefiderocol activity inAntimicrobial agents and chemotherapy · 2026Article
- Characterization of KPC-160, a novel Ω-loop-deleted KPC variant on a dual-copy plasmid that confers cefiderocol resistance.Antimicrobial agents and chemotherapy · 2026Article
- EnvZ/OmpR-driven cooperative behavior promotes cefiderocol resistance in a hanging-droplet evolution system.Science advances · 2026Article
- Genetic basis of cefiderocol resistance inMicrobiology spectrum · 2026Article
- Genomic analysis reveals multi-level resistance network linking oxidative stress pathway mutations to cefiderocol resistance and clonal evolution inFrontiers in cellular and infection microbiology · 2026Article
- Taming Superbugs: Current Progress and Challenges in Combating ESKAPE Pathogens.Pathogens (Basel, Switzerland) · 2025Review
- Siderophore cephalosporins.EcoSal Plus · 2025Review
- Review
- Cefiderocol: A Comprehensive Review of Chemistry, Mechanisms of Resistance, and Clinical Applications in the Era of Multidrug Resistance.Current microbiology · 2025Review
- In Vitro Activity of Cefiderocol Against Multi-Drug-Resistant Gram-Negative Clinical Isolates in Romania.Antibiotics (Basel, Switzerland) · 2025Article
- Combination Therapy of Cefiderocol and Polymyxin B Against Pseudomonas aeruginosa Keratitis Isolates In Vitro.Translational vision science & technology · 2025Article
- Sporadic cefiderocol resistance in Escherichia coli from the United Arab Emirates involves multifactorial mechanisms reversible by novel beta-lactamase inhibitors.Scientific reports · 2025Article
- Spontaneous Emergence of Cefiderocol Resistance inAntibiotics (Basel, Switzerland) · 2025Article
- Evaluating Antimicrobial Susceptibility Testing Methods for Cefiderocol: A Review and Expert Opinion on Current Practices and Future Directions.Antibiotics (Basel, Switzerland) · 2025Review
- Article
- Novel Variant of New Delhi Metallo-Beta-Lactamase (Antibiotics (Basel, Switzerland) · 2024Article
- Overexpression of β-lactamase genes (Antimicrobial agents and chemotherapy · 2024Article
- Some virulence genes are associated with antibiotic susceptibility in Enterobacter cloacae complex.BMC infectious diseases · 2024Article
- Conjugation to Native and Nonnative Triscatecholate Siderophores Enhances Delivery and Antibacterial Activity of a β-Lactam to Gram-Negative Bacterial Pathogens.Journal of the American Chemical Society · 2024Article
- Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCefiderocol (CFDC) is a novel siderophore-cephalosporin, effective against multidrug-resistant Gram-negative bacteria. As it has a siderophore side chain, it can utilize iron acquisition systems for penetration of the bacterial outer membrane. We aimed to elucidate the role of siderophores and iron uptake receptors in defining Klebsiella pneumoniae susceptibility to CFDC.
methodsInitially, 103 K. pneumoniae strains were characterized for susceptibility to different antibiotics including CFDC. CFDC minimum inhibitory concentrations (MIC) were determined in iron-depleted and iron-enriched conditions. Iron uptake genes including siderophores, their receptors, ferric citrate (fecA) and iron uptake (kfu) receptors were detected by PCR in all the strains. For 10 selected strains, gene expression was tested in iron-depleted media with or without CFDC treatment and compared to expression in iron-enriched conditions.
resultsCFDC exhibited 96.1% susceptibility, being superior to all the other antibiotics (MIC50: 0.5 and MIC90: 4 μg/ml). Only three strains (2.9%) were intermediately susceptible and a pandrug resistant strain (0.97%) was resistant to CFDC (MIC: 8 and 256 μg/ml, respectively). The presence of kfu and fecA had a significant impact on CFDC MIC, especially when co-produced, and if coupled with yersiniabactin receptor (fyuA). CFDC MICs were negatively correlated with enterobactin receptor (fepA) expression and positively correlated with expression of kfu and fecA. Thus, fepA was associated with increased susceptibility to CFDC, while kfu and fecA were associated with reduced susceptibility to CFDC. CFDC MICs increased significantly in iron-enriched media, with reduced expression of siderophore receptors, hence, causing less drug uptake.
conclusionIron acquisition systems have a significant impact on CFDC activity, and their altered expression is a factor leading to reduced susceptibility. Iron concentration is also a major player affecting CFDC susceptibility; therefore, it is essential to explore possible ways to improve the drug activity to facilitate its use to treat infections in iron-rich sites.
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