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.AimThis observational study aimed to probe the diversity of carbapenemase-producing E. coli (CP E. coli) ST131 across England.MethodsST131 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.ResultsThirty-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 clade 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).ConclusionWhen 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.
Highlights
The increasing incidence of antimicrobial resistance worldwide and a paucity of new drugs in development presents a major threat to the treatment of bacterial infections [1,2]
Temporal analysis showed that the average number of CP E. coli ST131 isolates submitted to Public Health England (PHE) on a monthly basis rose from 0.67 in 2014 (ST131 CP E. coli = 8), to 1.67 in 2015 (ST131 CP E. coli = 20), and to 1.83 in 2016
As a percentage of the total CP E. coli isolates across England, ST131 represented 4.5% in 2014 (CP E. coli = 177), 6.2% in 2015 (CP E. coli = 324) and 4.9% in the first half of 2016 (CP E. coli = 223). This increase in CP E. coli was linked to the number of KPC-2 producing isolates (mean/month: 2014 = 0.33; Figure 3 Antimicrobial resistance genes per Escherichia coli isolate (CP E.coli, England, 2014–2016: n = 39; non-CP E. coli: n = 188)
Summary
The increasing incidence of antimicrobial resistance worldwide and a paucity of new drugs in development presents a major threat to the treatment of bacterial infections [1,2]. The successive emergences of Escherichia coli with horizontally acquired CTX-M extended-spectrum beta-lactamases (ESBLs) and, more recently, carbapenemases, have heralded the advent of resistance to last-resort treatment options for many serious infections because of E. coli and other Enterobacterales. Clade C strains were characterised by distinct alleles for the genes gyrA (coding for gyrase) and parC (coding for topoisomerase) which impart elevated fluoroquinolone resistance (FQ-R) [1,2]. 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. 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
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