One Health Genomic Surveillance of Escherichia coli Demonstrates Distinct Lineages and Mobile Genetic Elements in Isolates from Humans versus Livestock

Abstract

Livestock have been proposed as a reservoir for drug-resistant Escherichia coli that infect humans. We isolated and sequenced 431 E. coli isolates (including 155 extended-spectrum β-lactamase [ESBL]-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1,517 E. coli bacteria associated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, suggesting that E. coli causing serious human infection had not directly originated from livestock. In contrast, we observed highly related isolates from the same animal species on different farms. Screening all 1,948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions in human and livestock isolates. Overall, we identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that within the confines of our sampling framework, there was limited evidence that antimicrobial-resistant pathogens associated with serious human infection had originated from livestock in our region.IMPORTANCE The increasing prevalence of E. coli bloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources of E. coli associated with serious human disease. E. coli from 1,517 patients with bloodstream infections were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was limited overlap in the mobile elements carrying these genes. Within the limitations of sampling, our findings do not support the idea that E. coli causing invasive disease or their resistance genes are commonly acquired from livestock in our region.

Keywords: ESBL; Escherichia coli; antimicrobial resistance; genomics; livestock.

FIG 1

(a) Map of the United Kingdom showing the locations for the human clinical isolates, with the East of England highlighted by a red box. (b) Map of the East of England showing the locations of farms (images indicate livestock species). (c) Maximum likelihood tree based on SNPs in the core genes of 1,948 E. coli isolates cultured from livestock farms, retail meat, and patients with bloodstream infection.

FIG 2

Network analysis of E. coli isolates cultured from livestock farms and patients with bloodstream infection. The results shown are limited to those isolate pairs identified in a pairwise comparison that differed by ≤15 or less SNPs in the core genome. The place of origin for each isolate pair are connected by lines, and the style of the line reflects the SNP distance. The asterisk indicates one ST69 human isolate from hospital 10 linked to two ST69 turkey isolates from farm 23 that differed by 10 and 12 SNPs, respectively. The number or hash sign indicates one ST1081 human isolate from hospital 5 linked to one ST1081 pig isolate from farm 4 (differed by 10 SNPs) and 2 ST1081 (probably duplicate) pig isolates from farm 2 that differed by 14 SNPs.

FIG 3

(a) Venn diagram displaying antibiotic resistance genes identified in 1,948 E. coli isolates cultured from livestock, meat, and patients with bloodstream infections. (b) Bubble graph showing the proportion of genes shared between E. coli from humans and livestock. The bottom graph shows an expanded view of very low prevalence genes that are clustered in the lower left-hand corner of the graph. The size of each bubble represents the number of isolates that the gene was identified in. Bubbles are colored by antibiotic class.

FIG 4

Dendrograms of mobile genetic element clusters identified for bla_CTX-M-1 (a), bla_CTX-M-15 (b), bla_TEM-1 (c), strA (d), strB (e), sul1 (f), sul2 (g), tetA (h), and tetB (i) in livestock, humans, and retail meat.