Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131

Abstract

Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131.

Occurrence of Clinically Important Lineages, Including the Sequence Type 131 C1-M27 Subclone, among Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Wastewater

“…2. The tree comprises three clades (A, B, and C) and four subgroups (C0, C1, C1-M27, and C2) within clade C, findings consistent with previous studies (13,14). Among the STC131 strains detected in the present study, four strains belonged to clade A and 11 strains belonged to clade C. Congruent with previous studies, strains belonging to clade C were characterized by the fimH30 allele and LNIV (S83L and D87N in GyrA and S80I and E84V in ParC) genotypes in QRDRs.…”

“…H41, H22, and H30 indicate the fimH (type 1 fimbrial adhesin gene) allele type, and most strains belonging to each clade are known to carry the corresponding fimH allele. Clade C contains C0, C1, and C2, which can be defined based on the positions in the whole-genome phylogeny (13). Previous studies reported that the bla CTX-M-15 -harboring C2/H30Rx is highly responsible for the pandemic of ExPEC strains that carry ESBLs (9,11,12).…”

GlobalEscherichia coliSequence Type 131 Clade withblaCTX-M-27Gene

“…Recent studies focusing on evolutionary history of ST131 suggested that C1/ H 30R and C2/ H 30Rx clades emerged ≈30 years ago, after their acquisition of gyrA -1AB and parC -1aAB alleles from C0/ H 30 (non-R) clade ( 27 , 28 ). The phylogeny and smaller numbers of SNPs in the C1-M27 clade (Figure 1) suggest that this clade was recently diverged from the C1/ H 30R.…”

The ST131 Escherichia coli H22 subclone from human intestinal microbiota: Comparison of genomic and phenotypic traits with those of the globally successful H30 subclone

“…According to the work of Ben Zakour et al [7], we determined the subclade B type of H 22 strain S250 and the clade C type of strain JJ1886 by direct blasting of the genes of the Flag-2 locus (Flag-2 locus from strain E. coli 042 [EMBL: CR 753847]), Phi3 (from strain EC958), and GI-PheV (from strain JJ1886) against the genome of strains S250 and JJI886. We then determined the type of subclade B displayed by strain S250 and the two other fecal H 22 strains by PCR using primers specific for the Flag-2 locus, Phi3, and GI-PheV (Additional file 1: Table S1) and our H 30-R fecal strains as a positive control.…”

“…It also revealed that subclone H 22 was the precursor of subclone H 30 and that separate F-type plasmids have shaped the evolution of subclone H 30 [2, 3, 5, 6]. The most recent ST131 E. coli phylogenetic reconstruction carried out by Ben Zakour et al using 3779 non-recombinant single nucleotide polymorphisms (SNP) found in the high quality genomes of 172 clade B and C strains, identified five B subclades, for which the independent evolutionary trajectories are characterized by successive insertions and a recombination from ancestral H 22 (subclade B1) [7]. Subclade B2 is characterized by a Flag-2 locus insertion, subclade B3 by a Flag-2 locus insertion and par-C2 recombination, subclade B4 by Flag-2 locus and GI-PheV insertions, and subclade B5 by Flag-2 locus and Phi3 insertions.…”