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

Cindy Liu, Maliha Aziz, Daniel Park, Zhenke Wu, Marc Stegger, Mengbing Li, Yashan Wang, Kara Schmidlin, Timothy Johnson, Benjamin Koch, Bruce Hungate, Lora Nordstrom, Lori Gauld, Brett Weaver, Diana Rolland, Sally Statham, Brantley Hall, Sanjeev Sariya, Gregg Davis, Paul Keim, James Johnson, Lance Price (2022+). Submitted.
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Summary

Background: Escherichia coli 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 E. coli strains from food animals to humans. However, the relative contribution of foodborne zoonotic E. coli (FZEC) to the human extraintestinal disease burden and the distinguishing characteristics of such strains remain undefined.

Methods: Using a comparative genomic analysis of a large collection of contemporaneous, geographically-matched clinical and meat-source E. coli isolates (n = 3,111), 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 E. coli isolates.

Findings: We estimated that approximately eight percent of human extraintestinal E. coli 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-H22 and ST58, appeared to have particularly high virulence potential.

Interpretation: Our findings imply that FZEC strains collectively cause more urinary tract infections than does any single non-E. coli uropathogenic species (e.g., Klebsiella pneumoniae), and that among human clinical E. coli isolates such strains numerically rival the leading human-associated extraintestinal pathogenic E. coli lineages. Our novel approach can be applied in other settings to identify the highest-risk FZEC strains, determine their sources, and inform new strategies to decrease the heavy public health burden imposed by extraintestinal E. coli infections.

RESEARCH IN CONTEXT Evidence before this study. Previous research dating back to the 1960s suggest that urinary tract infections could be caused by foodborne zoonotic E. coli (FZEC), but at the time that we initiated this study and at the time of submission, there were no reliable estimates of the proportion of human extraintestinal infections caused by FZEC strains (most recent Pubmed and Scopus reviews conducted on 06 July 2022).

Added value of this study. This paper describes a novel genomic/statistical approach for identifying host origins of E. coli strains. By applying this approach to a well-characterized collection of clinical E. coli isolates, we provide the first published estimate of the proportion of sporadic extraintestinal infections caused by FZEC strains in the United States.

Implications of all the available evidence. The results from this study suggest that a material portion of human extraintestinal infections, especially urinary tract infections, are caused by FZEC strains. This opens the possibility for reducing the burden of E. coli disease by preventing these strains from entering the food supply.