Emergence of enteroaggregative Escherichia coli within the ST131 lineage as a cause of extraintestinal infections

Abstract

Escherichia coli sequence type 131 (ST131) is a major cause of urinary and bloodstream infections and its association with extended-spectrum {beta}-lactamases (ESBL) significantly complicates treatment. Most notorious is its rapidly expanding H30-Rx clade (named for containing allele 30 of the type-1 fimbrial adhesin gene fimH and extensive antimicrobial resistance), which appears to have emerged in the United States due in part due to the acquisition of the ESBL-encoding blaCTX-M-15 gene and resistance to fluoroquinolones. However, non-H30 ST131 lineages with acquired CTX-M-type resistance genes also are emerging. Based on whole-genome analyses, we describe here the presence of an (fimH) H27 E. coli ST131 lineage that currently is causing an outbreak of community-acquired bacteremia and recurrent urinary tract infections (UTIs) in Denmark. This lineage has acquired both a virulence plasmid (pAA) that defines the enteroaggregative E. coli (EAEC) diarrheagenic pathotype and multiple genes associated with extraintestinal E. coli (ExPEC) that combined has made this particular ST131 lineage highly successful at colonizing its human host and cause recurrent UTI. Moreover, using a historic World Health Organization E. coli collection and publically available genome sequences, we identify a global H27 EAEC ST131 lineage dating back as far as 1998. Most H27 EAEC ST131 isolates harbor pAA or pAA-like plasmids, which analysis strongly imply was caused by a single ancestral acquisition. These findings illustrate the profound plasticity of this important pathogenic E. coli H27 lineage in general, and the genetic acquisitions of EAEC-specific virulence traits that likely confer an enhanced ability to cause intestinal colonization.\n\nImportanceThe E. coli ST131 lineage is a notorious extraintestinal pathogen. A signature characteristic of ST131 is its ability to asymptomatically colonize the gastrointestinal tract and then opportunistically cause extraintestinal infections, such as cystitis, pyelonephritis and urosepsis. In this study, we report a novel ST131 sublineage that has acquired the enteroaggregative diarrheagenic phenotype, spread across multiple continents and has been associated with multiple outbreaks of community-acquired bloodstream infections in Denmark. The strains ability to both cause diarrhea and colonize the human gastrointestinal tract may facilitate its dissemination and establishment in the community, whereas the strains clonal nature may facilitate targeted control strategies, such as vaccination.