Does AMR surveillance of surface water reflect AMR in humans? A genomic comparison of ESBL-producing Escherichia coli from surface water, healthy residents, and a clinical facility.

Wastewater antimicrobial resistance (AMR) surveillance is limited in many low- and middle-income countries where wastewater infrastructure is absent or inadequate. Surface water may provide an alternative for AMR surveillance in such settings. We investigated the resistome, virulome, and phylogenetic relationships of ESBL-producing Escherichia coli (ESBL-Ec) from surface water (SW), healthy residents (HR), and a clinical facility (CL) to determine whether SW isolates reflect human-associated AMR. During an eight-month longitudinal study in South Africa, 95 ESBL-Ec isolates (SW = 32, HR = 32, CL = 31) underwent whole-genome sequencing. Bioinformatics was used to characterise antimicrobial resistance genes (ARGs), virulence genes, sequence types (STs), phylogroups, and phylogenetic relationships. Seven phylogroups and 21 STs were identified. Phylogroups A, B1, and D and STs 10 and 38 occurred across all sources. Several clinically important lineages, including ST131, were shared between SW and HR isolates; no ST was unique to clinical isolates. Phylogenetic analysis revealed predominantly ST-driven clustering, with SW isolates showing greater similarity to HR isolates than to clinical isolates. Forty-five ARGs were detected, including 12 β-lactamase genes. blaCTX-M-15 was the dominant ESBL gene in all clinical isolates and in approximately half of SW and HR isolates. Resistance and virulence gene profiles were more frequently shared between SW and HR than between SW and CL isolates. Surface water did not fully reflect community and clinical ESBL-Ec populations but captured clinically relevant lineages and resistance determinants. These findings support SW monitoring as a complementary AMR surveillance approach in resource-limited settings lacking wastewater infrastructure.