Abstract
Background: Escherichia coli ST131, a global, high-risk clone, comprises fluoroquinolone resistance (FQ-R) mutations and CTX-M extended-spectrum beta-lactamases associated with the fimH30-encoding clades, C1 and C2. Further carbapenem resistance development in ST131 is a public health concern. Aim: This observational study aimed to probe the diversity of carbapenemase-producing E. coli (CP E. coli) ST131 across England. Methods: ST131 isolates were identified using whole-genome sequencing (WGS) data generated for all non-duplicate CP E. coli from human samples submitted to the national reference laboratory from January 2014 to June 2016. Antimicrobial resistance (AMR) gene content and single nucleotide polymorphism (SNP) data were compared against a published ST131 phylogeny and analysed alongside patient metadata. Results: Thirty-nine genetically diverse ST131 CP E. coli, from eight of nine regions, represented 10% of CP E. coli isolates sequenced. Ten and eight isolates were from the FQ-susceptible (FQ-S) clades A and B, while eight and 15 isolates belonged to the FQ-R clades C1 or C2, respectively. Seven distinct carbapenemases were identified: KPC-2 (21 isolates, 6 regions) frequently occurred among Glade C2 isolates (n=10). OXA-48-producers (10 isolates, 3 regions) were often from clade A (n =5). NDM-1 (n=4), NDM-5 (n=1), VIM-1 (n =1), VIM-4 (n =1) and OXA-181 (n =1) were also identified. Clade C2 isolates encoded more AMR genes than those from clades A (p=0.02), B (p =9.6 x 10(-3)) or C1 (p=0.03). Conclusion: When compared with its global predominance among ESBL-E. coli, ST131 represented a fraction of the CP E. coli received, belonging to diverse clades and encoding diverse carbapenemases. The greater accumulation of resistance genes in clade C2 isolates highlights the need for ongoing monitoring of this high-risk lineage.