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Cefiderocol resistance genes identified in environmental samples using functional metagenomics.
Remi Gschwind1, Mehdi Bonnet1,2, Anna Abramova3,4,5
1Université Paris Cité and Université Sorbonne Paris Nord, INSERM, IAME, 16 rue Henri Huchard, Paris F-75018, France.
The ISME Journal
|January 28, 2026
Summary
New cefiderocol resistance genes were discovered in environmental samples using functional metagenomics. This finding is crucial for improving antibiotic resistance surveillance and understanding the spread of resistance genes in the environment.
Area of Science:
- Environmental microbiology
- Molecular biology
- Public health
Background:
- Antibiotic resistance is a global health threat, exacerbated by environmental gene transfer.
- Cefiderocol, a last-line antibiotic, faces emerging resistance challenges.
- Existing databases lack characterization of cefiderocol resistance mechanisms.
Purpose of the Study:
- To identify and characterize novel cefiderocol resistance genes in environmental samples.
- To assess the prevalence and potential for spread of these genes.
- To improve antibiotic resistance surveillance strategies.
Main Methods:
- Functional metagenomics applied to diverse environmental samples (wastewater, freshwater, soil).
- Identification of genes conferring increased cefiderocol minimum inhibitory concentrations.
- Bioinformatic analysis to determine gene homologs and mobile genetic element association.
Main Results:
- Four novel cefiderocol resistance genes identified: three beta-lactamases (VEB-3, OXA-372 homolog, YbxI homolog) and a penicillin-binding protein homolog.
- These genes increased cefiderocol resistance to clinically relevant levels (1-4 mg/L).
- Three genes had homologs in pathogenic bacteria; blaVEB-3 was widespread in wastewater and linked to mobile genetic elements.
Conclusions:
- Functional metagenomics is essential for discovering uncharacterized antibiotic resistance mechanisms.
- Novel cefiderocol resistance genes are present in the environment, necessitating improved surveillance.
- Characterizing these genes will enhance antibiotic resistance gene databases and support One Health initiatives.
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