<i>Escherichia coli</i> Sequence Type 410 Is Causing New International High-Risk Clones

<i>Escherichia coli</i> sequence type 410 (ST410) has been reported worldwide as an extraintestinal pathogen associated with resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems. In the present study, we investigated national epidemiology of ST410 <i>E. coli</i> isolates from Danish patients. Furthermore, <i>E. coli</i> ST410 was investigated in a global context to provide further insight into the acquisition of the carbapenemase genes <i>bla</i>_OXA-181 and <i>bla</i>_NDM-5 of this successful lineage. From 127 whole-genome-sequenced isolates, we reconstructed an evolutionary framework of <i>E. coli</i> ST410 which portrays the antimicrobial-resistant clades B2/H24R, B3/H24Rx, and B4/H24RxC. The B2/H24R and B3/H24Rx clades emerged around 1987, concurrently with the C1/H30R and C2/H30Rx clades in <i>E. coli</i> ST131. B3/H24Rx appears to have evolved by the acquisition of the extended-spectrum β-lactamase (ESBL)-encoding gene <i>bla</i>_CTX-M-15 and an IncFII plasmid, encoding IncFIA and IncFIB. Around 2003, the carbapenem-resistant clade B4/H24RxC emerged when ST410 acquired an IncX3 plasmid carrying a <i>bla</i>_OXA-181 carbapenemase gene. Around 2014, the clade B4/H24RxC acquired a second carbapenemase gene, <i>bla</i>_NDM-5, on a conserved IncFII plasmid. From an epidemiological investigation of 49 <i>E. coli</i> ST410 isolates from Danish patients, we identified five possible regional outbreaks, of which one outbreak involved nine patients with <i>bla</i>_OXA-181- and <i>bla</i>_NDM-5-carrying B4/H24RxC isolates. The accumulated multidrug resistance in <i>E. coli</i> ST410 over the past two decades, together with its proven potential of transmission between patients, poses a high risk in clinical settings, and thus, <i>E. coli</i> ST410 should be considered a lineage with emerging "high-risk" clones, which should be monitored closely in the future.<b>IMPORTANCE</b> Extraintestinal pathogenic <i>Escherichia coli</i> (ExPEC) is the main cause of urinary tract infections and septicemia. Significant attention has been given to the ExPEC sequence type ST131, which has been categorized as a "high-risk" clone. High-risk clones are globally distributed clones associated with various antimicrobial resistance determinants, ease of transmission, persistence in hosts, and effective transmission between hosts. The high-risk clones have enhanced pathogenicity and cause severe and/or recurrent infections. We show that clones of the <i>E. coli</i> ST410 lineage persist and/or cause recurrent infections in humans, including bloodstream infections. We found evidence of ST410 being a highly resistant globally distributed lineage, capable of patient-to-patient transmission causing hospital outbreaks. Our analysis suggests that the ST410 lineage should be classified with the potential to cause new high-risk clones. Thus, with the clonal expansion over the past decades and increased antimicrobial resistance to last-resort treatment options, ST410 needs to be monitored prospectively.