Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131-H30Rx and ST131-H30R1 Strains

Escherichia coli sequence type 131 (ST131) predominates globally among multidrug-resistant (MDR) E. coli. We used whole-genome sequencing (WGS) to investigate 63 MDR E. coli isolates from 7 North Carolina community hospitals (2010-2015). Of these, 39 (62%) represented ST131, including 37 (95%) from the ST131-H30R subclone: 10 (27%) from its H30R1 subset, and 27 (69%) from its H30Rx subset. ST131 core genomes differed by a median of 15 single-nucleotide variants (SNVs) overall (range, 0-490), vs. only 7 within H30R1 (range, 3-12 SNVs) and 11 within H30Rx (range, 0-21). The four isolates with identical core genomes all were H30Rx. Epidemiological and clinical characteristics did not vary significantly by strain type, but many patients with MDR E. coli or H30Rx infection were critically ill and had poor outcomes. H30Rx isolates characteristically exhibited fluoroquinolone resistance and CTX-M-15 production, had a high prevalence of trimethoprim-sulfamethoxazole resistance (89%), sul1 (89%), and dfrA17 (85%), were enriched for specific virulence traits, and all qualified as extraintestinal pathogenic E. coli. The high overall prevalence of CTX-M-15 appeared possibly attributable to its association with the ST131-H30Rx subclone and IncF[F2:A1:B-] plasmids. Some phylogenetically clustered non-ST131 MDR E. coli isolates also had distinctive serotypes/fimH types, fluoroquinolone mutations, CTX-M variants, and IncF types. Thus, WGS analysis of our community hospital-source MDR E. coli isolates suggested ongoing circulation and differentiation of E. coli ST131 subclones, with clonal segregation of CTX-M variants, other resistance genes, Inc-type plasmids, and virulence genes.