Household Clustering of Escherichia coli Sequence Type 131 Clinical and Fecal Isolates According to Whole Genome Sequence Analysis

Abstract

Background. Within-household sharing of strains from the resistance-associated H30R1 and H30Rx subclones of Escherichia coli sequence type 131 (ST131) has been inferred based on conventional typing data, but it has been assessed minimally using whole genome sequence (WGS) analysis. Methods. Thirty-three clinical and fecal isolates of ST131-H30R1 and ST131-H30Rx, from 20 humans and pets in 6 households, underwent WGS analysis for comparison with 52 published ST131 genomes. Phylogenetic relationships were inferred using a bootstrapped maximum likelihood tree based on core genome sequence polymorphisms. Accessory traits were compared between phylogenetically similar isolates. Results. In the WGS-based phylogeny, isolates clustered strictly by household, in clades that were distributed widely across the phylogeny, interspersed between H30R1 and H30Rx comparison genomes. For only 1 household did the core genome phylogeny place epidemiologically unlinked isolates together with household isolates, but even there multiple differences in accessory genome content clearly differentiated these 2 groups. The core genome phylogeny supported within-household strain sharing, fecal-urethral urinary tract infection pathogenesis (with the entire household potentially providing the fecal reservoir), and instances of host-specific microevolution. In 1 instance, the household's index strain persisted for 6 years before causing a new infection in a different household member. Conclusions. Within-household sharing of E coli ST131 strains was confirmed extensively at the genome level, as was long-term colonization and repeated infections due to an ST131-H30Rx strain. Future efforts toward surveillance and decolonization may need to address not just the affected patient but also other human and animal household members.

Keywords: Escherichia coli infections; ST131; colonization; transmission; whole genome sequence.

Figure 1.

Pulsed-field gel electrophoresis profiles of 33 clinical and fecal isolates of Escherichia coli sequence type 131 (ST131) from the members of 6 households. Scale is % profile similarity. Only ST131 isolates and the corresponding subjects are included; other isolates, and subjects without an ST131 isolate, are not shown. All isolates were fluoroquinolone resistant. H30, clonal subset within the ST131-H30 clade (R1 = H30R1, Rx = H30Rx). Abbreviations; ESBL, extended-spectrum β-lactamase production; HH, household; ID, identifier; PFGE, pulsotype.

Figure 2.

Bootstrapped consensus core genome phylogeny for the 33 present household isolates and 47 comparison isolates of Escherichia coli sequence type 131 (ST131). The tree was based on 1000 bootstrapped maximum likelihood trees, retaining only those nodes that appeared in >70% of trees, and was rooted with strain CD306, which in the all-isolate phylogeny (data not shown) was basal. Clades H30R1 and H30Rx correspond, respectively, with clades C1 and C2 of Petty et al [8]. Branch lengths are meaningless. Household isolates are color-coded by household (1–6); comparison isolates, from Price et al [11], are shown in black. For the household isolates: boldface indicates clinical isolates; regular font indicates fecal isolates; underlining indicates fecal isolates from a clinical isolate's source host; and asterisks indicate the 6 household isolates that were included in Price et al [11], ie, JJ1886, JJ1887, JJ2547, CU758, CU799, and CD364 (which in Price et al was labeled as CD449). Dates are shown for the 2 households that underwent serial sampling.