One Health investigation of CTX-M type extended-spectrum beta-lactamase-producing Escherichia coli

Abstract

The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) poses a significant threat to public health, increasing human morbidity, mortality, and healthcare costs. CTX-M enzymes, encoded by blaCTX-M genes, have become the predominant type of ESBLs, conferring resistance to extended-spectrum beta-lactams. The One Health approach, which recognises the interconnectedness of the human, animal, food and environmental sectors, is crucial for understanding and combating the spread of CTX-M-producing E. coli. However, most studies have focused on limited One Health sectors, and a comprehensive cross-sectoral analysis of CTX-M-producing E. coli is required. Between 2018 and 2023, 445 CTX-M-producing E. coli isolates were collected from human blood, ready-to-eat food, raw meat, animals and food-processing surfaces in Hong Kong. All isolates underwent antimicrobial susceptibility testing, polymerase chain reaction and next-generation sequencing. For cross-sectoral analysis, we constructed a global dataset comprising 24,594 blaCTX-M-positive E. coli genomes and 2,310 blaCTX-M-carrying plasmids. Bioinformatic analyses were conducted to characterise genomic features, including CTX-M alleles, genomic population, blaCTX-M-carrying plasmids and shared blaCTX-M-containing sequences. We also compared these features across One Health sectors, incorporating genome metadata. For cross-sectoral investigation of CTX-M-producing E. coli in Hong Kong, a total of 445 unique blaCTX-M-positive E. coli isolates were collected, including 397 isolates from food samples (n = 2,893), animal samples (n = 217) and food-processing surfaces (n = 103), as well as 48 human blood isolates. The raw meat and animal sectors yielded the most CTX-M-producing E. coli isolates. The genetic diversity of CTX-M-producing E. coli in Hong Kong was substantial, with isolates classified into 16 major clusters. Notably, CTX-M-producing E. coli isolated from human bloodstream infections differed from those found in non-human sectors, exhibiting a predominant distribution in phylogroup B2, a higher prevalence of virulence factors, and a lower carriage of antibiotic resistance genes. Despite the overall diversity, several highly genetically similar E. coli pairs with fewer than 10 single nucleotide polymorphisms were observed across One Health sectors. For cross-sectoral investigation of global blaCTX-M dissemination among E. coli isolates and plasmids, we constructed a dataset of both CTX-M-producing E. coli (n = 24,594) and blaCTX-M-carrying plasmids (n = 2,310) across the human, animal, food and environmental sectors among six continents. Cross-sectoral analysis of the E. coli genomes revealed a high abundance of antibiotic resistance genes in isolates from the Asian animal sector. IncF plasmids emerged as key drivers of blaCTX-M dissemination with several plasmids exhibiting a capacity for cross-sectoral dissemination. While most E. coli lineages were predominantly human-associated, several demonstrated cross-sectoral dissemination potential. Analysis of blaCTX-M-carrying plasmids revealed most of plasmids were associated with human sectors except for blaCTX-M-1-carrying plasmids, which were more prevalent in non-human sectors. Shared genetic elements, particularly those associated with ISEcp1, IS26 and IS903, were indicators of cross-sectoral blaCTX-M gene dissemination. We comprehensively analysed the genetic data of blaCTX-M-positive E. coli and blaCTX-M-carrying plasmids across One Health sectors, shedding light on the genetic characterisation of CTX-M-producing E. coli from Hong Kong and the global dissemination of blaCTX-M genes.