Increasing resistance to third-generation cephalosporins and fluoroquinolones amongst uropathogenic Escherichia coli are of critical concern to public health. Resistance is mainly driven by extended-spectrum beta-lactamase (ESBL)-producing E. coli – particularly the sequence type (ST)131 C2/H30Rx sub-lineage, which is mostly responsible for pandemic cases. ST1193 is globally-disseminated and is second only to ST131 in terms of clinical prevalence. We sought to characterise the emergence of this important lineage with a comprehensive genomics approach.
Here, we used whole-genome sequencing to investigate 55 ST1193 genomes collected across Australia between 2007 and 2013. Long-read sequencing was used to assemble the complete reference genome MS10858 and determine the genomic context of genes encoding antimicrobial resistance and virulence factors in eight other isolates carrying blaCTX-M metallo-beta-lactamase genes. Well-characterised published genomes of strains from the same clonal complex (CC)14 (n=54) were used to contextualise our Australian dataset and investigate spatial clusters and lineage diversity.
Fluoroquinolone-resistant ST1193 are mediated by point mutations in gyrA, parC, and parE, distinguishing them from other lineages within CC14. Bayesian analysis predicted that fluoroquinolone-resistant ST1193 emerged in 1989. This coincides with the increase in human use of fluoroquinolones in Australia, after their inclusion in government-subsidised medications in 1988. ST1193 has two major clades with high intra-clade chromosomal similarity. Remarkably, the globally-distributed clade 1 is distinguished by recombination of a 30.4 kb region encompassing the capsular biosynthesis genes causing a switch from the K5 to K1 capsular antigen, which is associated with increased serum survivability. Assembly of MS10858 revealed an 11.5 kb composite transposon Tn6623 containing five resistance genes on an F-type plasmid, and an ISEcp1-blaCTX-M-15 element on an IncI1 plasmid. Nanopore sequencing of eight other isolates revealed a major role for ISEcp1 in mobilising CTX-M-type metallo-beta-lactamase genes, with both plasmid and chromosomal integrations observed.
This work describes a comprehensive genomic characterisation of ST1193 and identifies a single recombination event in the capsule locus, associated with the global dissemination of this fluoroquinolone-resistant UPEC clone.