Using source-associated mobile genetic elements to identify zoonotic extraintestinal infections.

A one-health perspective may provide new and actionable information about transmission. colonizes a broad range of vertebrates, including humans and food-production animals, and is a leading cause of bladder, kidney, and bloodstream infections in humans. Substantial evidence supports foodborne transmission of pathogenic strains from food animals to humans. However, the relative contribution of foodborne zoonotic (FZEC) to the human extraintestinal disease burden and the distinguishing characteristics of such strains remain undefined. Using a comparative genomic analysis of a large collection of contemporaneous, geographically-matched clinical and meat-source isolates ( = 3111), we identified 17 source-associated mobile genetic elements - predominantly plasmids and bacteriophages - and integrated them into a novel Bayesian latent class model to predict the origins of clinical isolates. We estimated that approximately 8 % of human extraintestinal infections (mostly urinary tract infections) in our study population were caused by FZEC. FZEC strains were equally likely to cause symptomatic disease as non-FZEC strains. Two FZEC lineages, ST131-22 and ST58, appeared to have particularly high virulence potential. Our findings imply that FZEC strains collectively cause more urinary tract infections than does any single non- uropathogenic species (e.g., ). Our novel approach can be applied in other settings to identify the highest-risk FZEC strains, determine their sources, and inform new one-health strategies to decrease the heavy public health burden imposed by extraintestinal infections.