Exploration of the genomic diversity of third-generation cephalosporin-resistant Escherichia coli in Australian clinical settings

Abstract Escherichia coli resistant to third-generation cephalosporins (3GCs) is a WHO priority pathogen due to its antimicrobial resistance (AMR). In high-income countries, such as Australia, 3GC-resistant E. coli are a common cause of extra-intestinal infections in both healthcare and community settings. Long-term targeted surveillance efforts of AMR in E. coli routinely identify E. coli as a leading pathogen in bacteraemic infections. To date, there has been limited detailed genomic analysis of the drug-resistant E. coli circulating in Australian clinical settings. Here, we sought to explore the genomic diversity of 3GC-resistant isolates (mediated by extended-spectrum beta-lactamase or AmpC), collected from four hospital networks in Melbourne, Australia. We establish the population structure, identifying ten main lineages in addition to multiple other sequence types, demonstrating 3GC resistance has emerged in multiple genetic backgrounds. We show diversity of accessory genome features, including surface antigens, AMR and plasmid profiles. A total of 117 serotypes and 47 capsular loci were detected, with diversity observed within and between main lineages. We identified 17 unique 3GC resistance mechanisms disseminated across the E. coli population, which co-occurred in different combinations of AMR genes and plasmid replicons. We explored the use of genomic clustering as an approach to detect different population dynamics, identifying 99 clusters of which only 15 had more than 5 isolates. This study provides a comprehensive snapshot of these drug-resistant E. coli in Australia over this time period and will serve as a baseline for future studies of clinical and community drug-resistant isolates in Australia.