From clinics to sewers: leveraging environmental surveillance and whole genome sequencing to inform transmission of ESBL- <i>Escherichia coli</i> in Switzerland

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL- E. coli ) is a major antimicrobial resistance concern spreading across human, animal, and environmental domains. To assess between-source transitions, we analyzed 762 ESBL- E. coli genomes collected from wastewater (used as a community shedding indicator), clinical settings, cattle, and wildlife across Switzerland (2021–2023). ST131 was the most prevalent sequence type (ST), and 76% of isolates carried resistance to at least two antibiotic classes in addition to β-lactams. Phylogenetic analysis showed isolates were interspersed across sources, yet genetically similar strains were more common within compartments. Clonal isolates (0 SNPs) were rarely shared ( n = 2) between wastewater and corresponding clinics. Ancestral state reconstruction revealed compartmentalization of isolates between wastewater and clinics across the whole phylogeny. However, this pattern disappears within human-associated ST131, ST69, and ST1193, highlighting exchange between clinics and communities. These findings show that wastewater surveillance captures community circulation of ESBL- E. coli, which overlaps with circulating clinically relevant strains. IMPORTANCE Extended-spectrum β-lactamase-producing Escherichia coli (ESBL- E. coli ) is a major antimicrobial resistance concern globally, with ready transmission between people, animals, and the environment. Understanding transmission patterns among reservoirs can help inform risks and inform intervention strategies. To date, surveillance is heavily reliant on aggregation of clinical data, resulting in limited insights on ESBL- E. coli circulation in the population. Wastewater-based surveillance has emerged as a powerful tool to understand epidemiology of antimicrobial resistance circulating in communities, thereby complementing clinical surveillance approaches. Here, we demonstrate integrated surveillance of ESBL- E. coli isolates across sectors using whole genome sequencing, providing an opportunity to understand exchange of bacterial isolates between clinics, communities, livestock, and wildlife.