Emergence of a carbapenem-resistant atypical uropathogenic Escherichia coli clone as an increasing cause of urinary tract infection.

Carbapenem-resistant Enterobacterales pose a critical global health threat, exemplified by increasing resistance of uropathogenic E. coli (UPEC) that cause urinary tract infections (UTIs). Here, we investigate the publicly available EnteroBase dataset and identify a signal of increasing UTI caused by phylogroup A E. coli sequence type 167 (ST167). Phylogenetic analysis of ST167 based on whole genome sequence data reveal three major clades (A, B, C), with clade C further resolving into several subclades, notably subclade C2 that possessed high carriage rates of carbapenem and cephalosporin resistance genes. Hierarchical clustering of core genome multi-locus sequence typing reveals ~77% of subclade C2 strains contain <20 allelic differences in 2,513 core genes and harbour two distinct group 1 capsule types, KL124 and KL30, likely originating from Klebsiella. Subclade C2 was predominantly sequenced in North America, and we provide evidence for clonal expansion since 2016. Analysis of UPEC virulence factors reveals complete loss of the type 1 fimbriae genes in strains from clades B and C. Two subclade C2 isolates exhibit significantly reduced capacity to colonise the bladder compared to the reference UPEC strain CFT073 in a murine UTI model. Collectively, our data identifies ST167 as an atypical UPEC clone associated with UTI.