Origin and Evolution of Hybrid Shiga Toxin-Producing and Uropathogenic Escherichia coli Strains of Sequence Type 141.

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