Pangenomic and functional domain comparison of enterotoxigenic Escherichia coli isolated from humans and swine: insights into host specificity

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is a common threat to humans and animals. Clinical ETEC strains display host tropism, usually driven by adherence and toxin-host interactions in the gut. Other virulence factors, metal acquisition mechanisms, and immune evasion strategies may also influence host specificity. Using publicly available genomes, we performed a pangenomic and functional comparison of 77 human- and swine-derived ETEC strains. Sequence types ST10 and ST4 found in both hosts, suggesting potential cross-host transmission. Phylogenetic analyses showed clustering mainly by ST, regardless of host or geography. Additionally, most functional domains were shared between hosts; however, human-derived strains carried exclusive domains related to adhesion, transposition, and toxins, whereas swine-derived strains harbored domains linked to stress response and metal binding. Notably, the PF09075 domain from the STb enterotoxin occurred only in swine-derived strains, despite previous reports in humans. Comparative analyses of STa (PF02048) and STb revealed no structural or functional homology but confirmed the swine-specific association of STb and greater sequence STa variability in human-derived strains. These findings indicate that sequence and functional differences in these enterotoxins contribute to ETEC host tropism, while ST patterns reveal possible epidemiological links between human and swine infections.