Genomic comparison of contemporaneous dog and human clinical E. coli isolates in Denmark reveals lineage-specific host associations and limited genomic relatedness across hosts.

Escherichia coli causes extraintestinal infections in humans and dogs, but the genomic relatedness of clinical lineages circulating in both hosts within the same region remains unclear. This study assessed the genomic relatedness between canine and human clinical isolates in the Zealand Region, Denmark, during 2022-2023. Ninety-five canine clinical E. coli isolates obtained from routine veterinary diagnostics were sequenced using Illumina MiSeq. Among 3832 contemporaneous human clinical genomes from the same region, all 1263 isolates belonging to the three most prevalent canine sequence types (ST372, ST73 and ST12) and the clinically important ST131 lineage were included in ST-specific phylogenomic comparisons. These STs accounted for 45 of 95 canine isolates. Nineteen mixed-host phylogenetic clusters comprised 29 of 45 (64.4%) canine and 62 of 1263 (4.9%) human isolates. Pairwise distances within clusters ranged from 20 to 2515 SNPs, but only three dog-human isolate pairs differed by ≤ 100 SNPs. Virulence gene composition was explained predominantly by sequence type (82.4% of variation), whereas host origin explained only 3%; antimicrobial resistance gene profiles frequently differed within clusters. ST372 was strongly canine-associated, with a major mixed-host cluster carrying the canine-associated pdu operon. ST12 showed extensive cross-species clustering and a uniform serotype, consistent with a host-generalist population; ST73 comprised heterogeneous sublineages with limited host overlap; and the three canine ST131 isolates belonging to clade B clustered with only 1.4% of human ST131 isolates despite partially overlapping avian-associated markers. Overall, these findings indicate lineage-specific host associations with only few closely related dog-human isolate pairs within the four selected lineages.