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Hybrid  E. coli  pathotypes are representing emerging public health threats with enhanced virulence from different pathotypes. Hybrids of Shiga toxin-producing and enterotoxigenic  E. coli  (STEC/ETEC) have been reported to be associated with diarrheal disease and hemolytic uremic syndrome (HUS) in humans. Here, we identified and characterized four clinical STEC/ETEC hybrids from diarrheal patients with or without fever or abdominal pain and healthy contact in Sweden. Rare  stx2  subtypes were present in STEC/ETEC hybrids. Stx2 production was detectable in  stx2a  and  stx2e  containing strains. Different copies of ETEC virulence marker,  sta  gene, were found in two hybrids. Three  sta  subtypes, namely,  sta1 ,  sta4  and  sta5  were designated, with  sta4  being predominant. The hybrids represented diverse and rare serotypes (O15:H16, O187:H28, O100:H30, and O136:H12). Genome-wide phylogeny revealed that these hybrids exhibited close relatedness with certain ETEC, STEC/ETEC hybrid and commensal  E. coli  strains, implying the potential acquisition of Stx-phages or/and ETEC virulence genes in the emergence of STEC/ETEC hybrids. Given the emergence and public health significance of hybrid pathotypes, a broader range of virulence markers should be considered in the  E. coli  pathotypes diagnostics, and targeted follow up of cases is suggested to better understand the hybrid infection.

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Molecular Characterization and Comparative Genomics of Clinical Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains in Sweden