Origin and evolution of hybrid Shiga toxin-producing and uropathogenic (STEC/UPEC) Escherichia coli of sequence type 141

Gati NS, Middendorf-Bauchart B, Bletz S, Dobrindt U, Mellmann A

Abstract

Hybrid Shiga toxin-producing and uropathogenic Escherichia coli (STEC/UPEC) of multilocus sequence type (ST) 141 cause both urinary tract infections and diarrhea in humans and are phylogenetically positioned between STEC and UPEC.We used comparative genomics of 85 temporal and spatial diverse ST141 E. coli strains including 14 STEC/UPEC hybrids collected in Germany (n=13) and USA (n=1) to reconstruct their molecular evolution.Whole genome sequencing data showed that 89% of ST141 E. coli strains were either STEC/UPEC hybrids or contained a mixture of virulence genes from other pathotypes. Core genome analysis and ancestral reconstruction revealed that ST141 E. coli clustered into two lineages that evolved from a common ancestor in mid-19th century. The STEC/UPEC hybrid emerged ∼100 years ago by acquiring stx-prophage, which integrated into previously unknown insertion site rcsB-rcsD, followed by the insertion of a Pathogenicity Island similar to PAI II of UPEC strain 536 (PAI II536-like). The two variants of the PAI II536-like were associated with tRNA genes leuX and pheU, respectively. Finally, microevolution within the PAI II536-like and acquisition of the EHEC plasmid were observed.Our data suggest that intestinal/extraintestinal pathogenic E. coli (IPEC/ExPEC) hybrids are widespread and selection pressure within ST141 E. coli population led to the emergence of the STEC/UPEC hybrid as a clinically important subgroup. We hypothesize that ST141 E. coli serve as a ‘melting pot' for pathogroup conversion between IPEC and ExPEC, contrasting the classical theory of pathogen emergence from non-pathogen and corroborating our recent phenomenon of heteropathogenicity among pathogenic E. coli.