Objectives: We performed a One Health surveillance in Hanoida region with a high-density human population and livestock production, and a recognized hotspot of animal-associated antimicrobial resistance (AMR)dto study the contribution of bla CTX-M -carrying Escherichia coli and plasmids from foodanimal sources in causing human community-acquired urinary tract infections (CA-UTIs). Methods: During 2014e2015, 9090 samples were collected from CA-UTI patients (urine, n ¼ 8564), pigs/ chickens from farms and slaughterhouses (faeces, carcasses, n ¼ 448), and from the slaughterhouse environment (surface swabs, water, n ¼ 78). E. coli was identified in 2084 samples. Extended-spectrum blactamase (ESBL) production was confirmed in 235 and bla CTX-M in 198 strains by PCR with short-read plasmid sequencing. Fourteen strains were long-read sequenced to enable plasmid reconstruction. Results: The majority of the ESBL-producing E. coli strains harboured bla CTX-M (n ¼ 198/235, 84%). High clonal diversity (48 sequence types, STs) and distinct, dominant STs in human sources (ST1193, n ¼ 38/ 137; ST131, n ¼ 30/137) and non-human sources (ST155, n ¼ 25/61) indicated lack of clonal transmission between habitats. Eight bla CTX-M variants were identified; five were present in at least two sample sources. Human and food-animal strains did not show similar plasmids carrying shared bla CTX-M genes. However, IS6 elements flanking ISEcp1ebla CTX-M eorf477/IS903B structures were common across habitats. Conclusions: In this study, animal-associated bla CTX-M E. coli strains or bla CTX-M plasmids were not direct sources of CA-UTIs or ESBL resistance in humans, respectively, suggesting evolutionary bottlenecks to their adaptation to a new host species. Presence of common IS6 elements flanking bla CTX-M variants in different plasmid backbones, however, highlighted the potential of these transposable elements for AMR transmission either within or across habitats.