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.

The rise in rates of human infection caused by vancomycin-resistant Enterococcus faecium (VREfm) strains between 1988 to the 2000s in Europe was suggested to be associated with acquisition from livestock. As a result, the European Union banned the use of the glycopeptide drug avoparcin as a growth promoter in livestock feed. While some studies reported a decrease in VREfm in livestock, others reported no reduction. Here, we report the first livestock VREfm prevalence survey in the UK since 2003 and the first large-scale study using whole-genome sequencing to investigate the relationship between E. faecium strains in livestock and humans. We found a low prevalence of VREfm in retail meat and limited evidence for recent sharing of strains between livestock and humans with bloodstream infection. There was evidence for limited sharing of genes encoding antibiotic resistance between these reservoirs, a finding which requires further research.

Background Klebsiella pneumoniae is a human, animal, and environmental commensal and a leading cause of nosocomial infections, which are often caused by multiresistant strains. We evaluate putative sources of K. pneumoniae that are carried by and infect hospital patients. Methods We conducted a 6-month survey on 2 hematology wards at Addenbrooke’s Hospital, Cambridge, United Kingdom, in 2015 to isolate K. pneumoniae from stool, blood, and the environment. We conducted cross-sectional surveys of K. pneumoniae from 29 livestock farms, 97 meat products, the hospital sewer, and 20 municipal wastewater treatment plants in the East of England between 2014 and 2015. Isolates were sequenced and their genomes compared. Results Klebsiella pneumoniae was isolated from stool of 17/149 (11%) patients and 18/922 swabs of their environment, together with 1 bloodstream infection during the study and 4 others over a 24-month period. Each patient carried 1 or more lineages that was unique to them, but 2 broad environmental contamination events and patient–environment transmission were identified. Klebsiella pneumoniae was isolated from cattle, poultry, hospital sewage, and 12/20 wastewater treatment plants. There was low genetic relatedness between isolates from patients/their hospital environment vs isolates from elsewhere. Identical genes encoding cephalosporin resistance were carried by isolates from humans/environment and elsewhere but were carried on different plasmids. Conclusion We identified no patient-to-patient transmission and no evidence for livestock as a source of K. pneumoniae infecting humans. However, our findings reaffirm the importance of the hospital environment as a source of K. pneumoniae associated with serious human infection.

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local

Running title: One Health genomic surveillance of Escherichia coli 25 2 ABSTRACT 26 Livestock have been proposed as a reservoir for drug-resistant Escherichia coli that infect 27 humans. We isolated and sequenced 431 E. coli (including 155 ESBL-producing isolates) 28 from cross-sectional surveys of livestock farms and retail meat in the East of England. These 29 were compared with the genomes of 1517 E. coli associated with bloodstream infection in the 30 United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and 31 patient isolates were genetically distinct, indicating that E. coli causing serious human 32 infection do not directly originate from livestock. By contrast, we observed highly related 33 isolates from the same animal species on different farms. Analysis of accessory (variable) 34 genomes identified a virulence cassette associated previously with cystitis and neonatal 35 meningitis that was only present in isolates from humans. Screening all 1948 isolates for 36 accessory genes encoding antibiotic resistance revealed 41 different genes present in variable 37proportions of humans and livestock isolates. We identified a low prevalence of shared 38 antimicrobial resistance genes between livestock and humans based on analysis of mobile 39 genetic elements and long-read sequencing. We conclude that in this setting, there was 40 limited evidence to support the suggestion that antimicrobial resistant pathogens that cause 41 serious infection in humans originate from livestock. 42 43 44 45 46 47 48 Importance 51The increasing prevalence of E. coli bloodstream infections is a serious public health 52 problem. We used genomic epidemiology in a One Health study conducted in the East of 53England to examine putative sources of E. coli associated with serious human disease. E. 54 coli from 1517 patients with bloodstream infection were compared with 431 isolates from 55 livestock farms and meat. Livestock-associated and bloodstream isolates were genetically 56 distinct populations based on core genome and accessory genome analyses. Identical 57 antimicrobial resistance genes were found in livestock and human isolates, but there was little 58 overlap in the mobile elements carrying these genes. In addition, a virulence cassette found in 59 humans isolates was not identified in any livestock-associated isolate. Our findings do not 60 support the idea that E. coli causing invasive disease or their resistance genes are commonly 61 acquired from livestock. 62 128 Genomic comparison of E. coli from patients with bloodstream infection, livestock, and 129 retail meat. We combined and compared the 1517 human invasive with the 431 livestock-130 associated genomes. Analysis of the 1948 genomes identified 331 multilocus sequence types 131 (STs), 44 clonal complexes (CCs) and 149 singletons (STs that did not share alleles at six out 132 of seven loci with any other STs). Most STs were host-specific, with 192 human-specific STs 133 (1261/1517 isolates, 83%), 98 livestock-specific STs (225/411 isolates, ...