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Extended-spectrum cephalosporinase producing (ESC) E. coli are regarded as key indicator microorganisms of antimicrobial resistance (AMR), calling for a One Health integrated global surveillance strategy. Wildlife is exposed to antibiotic contaminants and/or resistant bacteria that have been released into the environment, potentially acting as reservoirs and spreaders of resistance genes as well as sentinels of anthropogenic pressure. Monitoring AMR in wildlife has become crucial in determining anthropogenic environmental impacts as well as transmission routes. In this study, we determined the occurrence and potential sources of ESC E. coli in 218 Eurasian griffon vultures (Gyps fulvus) foraging regularly on human waste disposed at a dumpsite in north-eastern Spain. Minimal inhibitory concentration for 14 different antimicrobials was performed to evaluate the phenotype of the isolates, and whole genome sequencing was carried out to investigate lineages and plasmids harbouring ESC genes. Our sequences were compared to previously published Spanish sequences of human, animal, and wildlife origin. We report a high prevalence of CTX-M-15, as well as the presence of other resistance genes such as OXA-10, CTX-M-27, and CTX-M-65 which are rarely described in European livestock, suggesting a human origin. The isolates also carried a diverse range of additional AMR genes for a broad spectrum of drug families, with the majority being multi-drug resistant. The phylogenomic analyses suggests the transmission of high-risk lineages from humans to vultures, with 49 % of our isolates matching the most common extraintestinal pathogenic E. coli (ExPEC) lineages described in humans worldwide, including ST131, ST10 and ST58. We conclude that anthropogenically altered habitats, such as landfills, are hotspots for the acquisition and spread of high-risk ESC E. coli lineages associated with hospital infections. Measures must be implemented to limit their spread into natural environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)