Using source-associated mobile genetic elements to identify zoonotic extraintestinal E. coli infections
Cindy M. Liu,
Maliha Aziz,
Daniel E. Park,
Zhenke Wu,
Marc Stegger,
Mengbing Li,
Yashan Wang,
Kara Schmidlin,
Timothy J. Johnson,
Benjamin J. Koch,
Bruce A. Hungate,
Lora Nordstrom,
Lori Gauld,
Brett Weaver,
Diana Rolland,
Sally Statham,
Brantley Hall,
Sanjeev Sariya,
Gregg S. Davis,
Paul S. Keim,
James R. Johnson,
Lance B. Price
Affiliations
Cindy M. Liu
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA; The Pathogen and Microbiome Institute, Department of Biological Sciences, Northern Arizona University, Room 210 Building 56, Applied Research & Development, 1395 S Knoles Drive, Flagstaff, AZ 86011, USA
Maliha Aziz
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA
Daniel E. Park
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA
Zhenke Wu
Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Michigan Institute for Data Science (MIDAS), University of Michigan, 500 Church Street, Suite 600, Ann Arbor, MI 48109, USA
Marc Stegger
Department of Bacteria, Parasites and Fungi, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen, Denmark
Mengbing Li
Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
Yashan Wang
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA
Kara Schmidlin
Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA
Timothy J. Johnson
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1365 Gortner Ave, St Paul, MN 55108, USA
Benjamin J. Koch
Center for Ecosystem Science and Society, Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA
Bruce A. Hungate
Center for Ecosystem Science and Society, Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA
Lora Nordstrom
Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA
Lori Gauld
Flagstaff Medical Center, 1200 N. Beaver St. Flagstaff, AZ 86001, USA
Brett Weaver
Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA
Diana Rolland
Flagstaff Medical Center, 1200 N. Beaver St. Flagstaff, AZ 86001, USA
Sally Statham
Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA
Brantley Hall
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
Sanjeev Sariya
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA
Gregg S. Davis
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA
Paul S. Keim
The Pathogen and Microbiome Institute, Department of Biological Sciences, Northern Arizona University, Room 210 Building 56, Applied Research & Development, 1395 S Knoles Drive, Flagstaff, AZ 86011, USA; Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA
James R. Johnson
Minneapolis Veterans Affairs Health Care System, 1 Veterans Dr, Minneapolis, MN 55417, USA
Lance B. Price
Antibiotic Resistance Action Center, Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, 800 22nd Street NW, Washington, DC 20052, USA; Division of Pathogen Genomics, Translational Genomics Research Institute (TGen), 3051 W Shamrell Blvd, Flagstaff, AZ 86005, USA; Corresponding author at: Antibiotic Resistance Action Center, Milken Institute School of Public Health, George Washington University, Science & Engineering Hall, 800 22nd Street NW, 7th Floor - Office 7590, Washington, DC 20052, USA.
A one-health perspective may provide new and actionable information about Escherichia coli transmission. E. 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. Using a comparative genomic analysis of a large collection of contemporaneous, geographically-matched clinical and meat-source E. coli isolates (n = 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 E. coli isolates. We estimated that approximately 8 % 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. 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). 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 E. coli infections.
