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

Escherichia coli sequence type 131 (ST131) is a major cause of urinary and bloodstream infections. Its association with extended-spectrum ß-lactamases (ESBLs) significantly complicates treatment. Its best-described component is the rap-idly expanding H30Rx clade, containing allele 30 of the type 1 fimbrial adhesin gene fimH. This lineage appears to have emerged in the United States and spread around the world in part due to the acquisition of the ESBL-encoding bla_CTX-M-15 gene and resistance to fluoroquinolones. However, non-H30 ST131 sublineages with other acquired CTX-M-type resistance genes are also emerging. Based on whole-genome analyses, we describe here the presence of an (fimH) H27 E. coli ST131 sublineage that has recently caused an outbreak of community-acquired bacteremia and recurrent urinary tract infections (UTIs) in Denmark. This sublineage has acquired both a virulence plasmid (pAA) that defines the enteroaggregative E. coli (EAEC) diarrhea-genic pathotype and multiple genes associated with extraintestinal E. coli (ExPEC); combined, these traits have made this particular ST131 sublineage successful at col-onizing its human host and causing recurrent UTI. Moreover, using a historic World Health Organization (WHO) E. coli collection and publicly available genome se-quences, we identified a global H27 EAEC ST131 sublineage that dates back as far as 1998. Most H27 EAEC ST131 isolates harbor pAA or pAA-like plasmids, and our analysis strongly implies a single ancestral acquisition among these isolates. These find-ings illustrate both the profound plasticity of this important pathogenic E. coli ST131 H27 sublineage and genetic acquisitions of EAEC-specific virulence traits that likely confer an enhanced ability to cause intestinal colonization. IMPORTANCE E. coli ST131 is an important extraintestinal pathogenic lineage. A sig-nature characteristic of ST131 is its ability to asymptomatically colonize the gastrointestinal tract and then opportunistically cause extraintestinal infections, such as cystitis, pye-lonephritis, and urosepsis. In this study, we identified an ST131 H27 sublineage that has acquired the enteroaggregative diarrheagenic phenotype, spread across multiple conti-nents, and caused multiple outbreaks of community-acquired ESBL-associated bloodstream infections in Denmark. The strain’s ability to both cause diarrhea and innocuously colonize the human gastrointestinal tract may facilitate its dissemination and establishment in the community.