Introduction. Increasing resistance to third-generation cephalosporins (3GCs) amongst uropathogenic Escherichia coli are of critical concern to public health. Resistance is driven by extended-spectrum β-lactamase (ESBL)-producing E. coli - particularly those from the pandemic sequence type (ST)131 C2/H30Rx sub-lineage.
Methods. Here, we used whole-genome sequencing (WGS) to perform a retrospective epidemiological investigation of 582 ESBL-producing E. coli collected from several health districts in New Zealand between 1997 and 2014.
Results. Consistent with global findings, 57.6% (n=335/582) and 35.1% (n=204/582) of strains contained genes from the blaCTX-M-1 group and blaCTX-M-9 group, respectively, which confer resistance to 3GCs. The overall population was dynamic, covering 66 distinct lineages. New Zealand historically observed a relatively low frequency of ESBL-producing E. coli until the emergence and dominance of an O8:H9 ST410 clone that caused a prolonged outbreak in Hawkes Bay in 2001 (n=37/63 total strains collected in 2001, 58.7%). The assembly of an O8:H9 ST410 representative from long-reads places blaCTX-M-15, blaOXA-1, and blaTEM-1B alongside genes encoding resistance to aminoglycosides, fluoroquinolones, chloramphenicol, and tetracyclines within a 25 kb resistance island, which is flanked by TnAs3/IS15 and Tn5403, on a 91,656 bp F-type [F2:A-:B-] plasmid. All ST410 strain form the 2001 Hawkes Bay cluster carry this 25 kb resistance island. By 2007, ST131 (n=48/136 total strains collected in 2007, 35.3%) had completely displaced ST410 (n=4/136, 2.9%) as the dominant ESBL-producing lineage, where most strains represent the C2/H30Rx sub-lineage (n=26/48, 54.2%).
Conclusions. We confirm the clonal basis for ESBL-E. coli by demonstrating intraspecific competition between different lineages, before ESBL-producing ST131 emerged in the late 1990s and became dominant in 2007. We also demonstrate that blaCTX-M variants are not confined to ST131 and that convergence is associated with the emergence and dissemination of clonal lineages resistant to 3GCs in New Zealand. This investigation emphasises the value of combining WGS with epidemiology, allowing for detection of potential outbreaks and evidence-based interventions to prevent further emerging resistance.