Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131- H 30Rx and ST131- H 30R1 Strains

Abstract

Escherichia coli sequence type 131 (ST131) predominates globally among multidrug-resistant (MDR) E. coli strains. We used whole-genome sequencing (WGS) to investigate 63 MDR E. coli isolates from 7 North Carolina community hospitals (2010 to 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 (range, 0 to 490) singlenucleotide variants (SNVs) overall versus only 7 within H30R1 (range, 3 to 12 SNVs) and 11 within H30Rx (range, 0 to 21). The four isolates with identical core genomes were all 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 trimethoprimsulfamethoxazole resistance (89%), sul1 (89%), and dfrA17 (85%), and were enriched for specific virulence traits, and all qualified as extraintestinal pathogenic E. coli. The high overall prevalence of CTX-M-15 appeared to be possibly attributable to its association with the ST131-H30Rx subclone and IncF[F2:A1:BϪ] 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.

Genomic Epidemiology ofEscherichia coliIsolates from a Tertiary Referral Center in Lilongwe, Malawi

“…This is consistent with global trends that suggest that the highly drug-resistant E. coli ST131, associated with the bla CTX-M- 15 gene, has been increasing in prevalence. [9][10][11] [15][16][17][18] There is some subtle structure within ST131, with isolates from this study that are primarily localized on a branch with a longer internal branch length, which may suggest the seeding and expansion locally in central Malawi ( Figure 1 ). Another difference from previous work is the higher number of ST410 isolates in this study, which carried the bla CTX-M-15 gene at the highest frequency of all the sequence types.…”

“…[14] CTX-M-15 is strongly associated with ST131. [15][16][17][18] The global spread of ESBL-E. coli is largely attributed to the dissemination of E. coli strains carrying the bla CTX-M- 15 gene, especially E. coli O25b:H4-ST131. [11] Previously, three major lineages of ST131 were identified that differed mainly based on their fimH alleles: A (mainly fimH41), B (mainly fimH22) and C (mainly fimH30).…”

Dominance of ST131Escherichia colicarryingblaCTX-Min patients with bloodstream infections caused by cephalosporin-resistant strains in Australia, New Zealand and Singapore: whole genome analysis of isolates from a randomised trial

“…Previous work, mainly including isolates from North America, suggested that the H 30-R/C1 clade of ST131 most commonly carry IncF type F1:A2:B20 plasmids and the H 30-Rx/C2 clade are associated with IncF type F2:A1:B-plasmids. 17-19 In this cohort, plasmid types were associated with different sub-lineages of ST131. For instance, IncF type F31:A4:B1 or F36:A4:B1 plasmids were most frequently seen in clade C2, whereas IncF type F2:A1:B-were only seen in a single clade C1 strain.…”

“…8 Specific Incompatibility (Inc) F-type plasmids have also been described in association with fluoroquinolone-resistant ST131- H 30 clades, with IncF type F1:A2:B20 plasmids associated with the H 30-R/C1 clade and IncF type F2:A1:B-plasmids associated with the H 30-Rx/C2 clade. 17-19…”

First Indian report on Genome-wide Comparison of Multidrug-ResistantEscherichia colifrom Blood Stream Infections

“…Also, AMR among E. coli is increasingly reported for fluoroquinolones and third- and fourth-generation cephalosporins. Sequence type 131 (ST131) predominates globally among such MDR E. coli strains [11].…”