One Health in Eastern Africa: No barriers for ESBL producing E. coli transmission or independent antimicrobial resistance gene flow across ecological compartments

The One Health paradigm considers the interdependence of human, animal and environmental health. In high-income countries, limited evidence has been found from recent studies to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, and we are all interconnected it would be important to know if closer interaction of humans with animals and the environment in low-income present a contrasting picture. We used whole genome sequencing to investigate the genomic diversity and to infer transmission of extended spectrum beta-lactamase producing Escherichia coli (ESBL-Ec) between different ecological niches (humans, animals and the environment). We found high diversity of ESBL-Ec with 172 genomic clusters and 167 sequence types identified from 2,344 genomes. Common ESBL genes, blaCTX-M-15 (67.6%) and blaCTX-M-27 (14.2%) were carried on a complex network of different plasmids, presenting multiple pathways for dissemination and revealing the high force of selection. Using fine-scale genomic clustering across multiple thresholds ranging from 0 to 20 single nucleotide polymorphisms, we found that genomes isolated from humans, animals and the environment formed overlapping clusters, indicating recent ESBL-Ec transmission and co-circulation both within and between ecological compartments. These findings demonstrate that the One Health approach is highly relevant to tackling AMR in low-income settings, and therefore critical to consider if we are to address the rise of AMR globally.