Using metagenomics to find causes of antibiotic resistance

Map showing the geographic locations of samples included in functional metagenomics studies of cefiderocol resistance and the relative abundance of the genes identified using functional metagenomics in whole metagenome reads (if at least one had a relative abundance >0 in sequencing reads). Figure 5 of Gschwind et al.

Misuse and overuse of antimicrobials have led to a global health crisis: antimicrobial resistance (AMR), including multidrug-resistant superbugs. Common misconceptions that contribute to the problem have proven difficult to dispel; for example, 30% of Europeans believe that antibiotics are effective against colds (Eurobarometer 2022). One important arm of the multipronged strategy to tackle AMR is surveillance, but the current focus on clinical settings is too narrow. Microbes – including bacteria carrying antibiotic resistance genes (ARGs) – are everywhere, and environments like wastewater are hotspots for ARG exchange. A recent preprint, conducted as part of the SEARCHER project, used metagenomics and functional metagenomics on environmental samples to identify genes conferring resistance to cefiderocol, a last-resort antibiotic used against multidrug-resistant bacteria. Metagenomics is a technique that analyzes all the genetic material in a complex environmental sample, enabling identification of known ARGs. Functional metagenomics goes a step further, identifying ARGs based on their activity rather than their sequence. The authors used functional metagenomics to analyze freshwater, wastewater, and soil samples from Sweden, Germany, and Pakistan. By expressing sampled DNA in cefiderocol-sensitive host bacteria exposed to the antibiotic, they uncovered four ARGs not previously linked to cefiderocol resistance, two of which are not in current ARG databases. The paper showcases the importance of a ‘One Health’ surveillance strategy – i.e., one that recognizes the interconnectedness of human health, animal health, and the environment – to provide early warning of emerging AMR threats.


Environmental reservoir of resistance genes for the last resort antibiotic Cefiderocol
In bioRxiv, 28 May 2025

From the group of Etienne Ruppé, INSERM, France, and collaborators at the SEARCHER (Surveillance for Emerging Antimicrobial Resistance through Characterization of the uncharted Environmental Resistome) program.

Snippet by Katrina Woolcock.

Image credit: Figure 5 from Gschwind et al. cited above (CC BY-NC-ND).

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