Extended-spectrum β-lactamase–producing Escherichia coli are globally disseminated pathogens whose success is driven by clonal expansion and horizontal gene transfer. However, the population structure and evolutionary relationships of these organisms in the United Arab Emirates remain insufficiently characterized. In this study, we applied a population genomic and phylogenomic approach to investigate ESBL-producing E. coli causing bloodstream infections and their genetic relatedness to strains from non-human reservoirs within a One Health framework. Forty-five ESBL-producing E. coli isolates recovered from bloodstream infections between 2021 and 2024 were analyzed, with whole-genome sequencing performed on 29 representative isolates. Genomic analyses revealed the predominance of internationally disseminated high-risk lineages, particularly sequence types ST131 and ST1193, largely associated with the ESBL gene bla CTX-M-15 . Conserved genetic contexts of bla CTX-M-15 in these lineages suggested stable vertical inheritance, whereas greater diversity of mobile genetic elements was observed among non-ST131 isolates, indicating ongoing horizontal gene transfer. Additional resistance determinants, including bla DHA-1 , bla SHV-12 , and notably the carbapenemase gene bla NDM-5 , contributed to multidrug-resistant genotypes, indicating the coexistence of ESBL and carbapenemase activity in a subset of isolates. Phylogenomic comparisons based on core genome variation demonstrated close genetic relatedness between clinical isolates and E. coli from food, poultry, and environmental sources in the United Arab Emirates. These findings indicate that bloodstream infections are associated with shared circulating ESBL-producing E. coli lineages exhibiting genetic relatedness across human and non-human reservoirs. The results highlight the evolutionary connectivity of E. coli populations and emphasize the importance of integrated genomic surveillance to track and limit the spread of multidrug-resistant pathogens. • High multidrug resistance detected among ESBL-producing E. coli bloodstream isolates. • WGS revealed dominance of high-risk lineages ST131 and ST1193 in the UAE. • bla CTX-M-15 identified as the predominant ESBL gene with conserved genetic contexts. • bla NDM-5 detected in a clinical isolate, signaling emerging carbapenem resistance. • Phylogenomics linked clinical isolates to food, animal, and environmental reservoirs.
Khalifa et al. (Sun,) studied this question.