Escherichia coli ST410, causing new international high-risk clones

Abstract: Escherichia coli sequence type 410 (ST410) has been reported worldwide as an extra-intestinal pathogen associated with resistance to fluoroquinolones, third-generation cephalosporins and carbapenems. In the present study we investigated national epidemiology of ST410 E. coli isolates from Danish patients. Furthermore, E. coli ST410 was investigated in a global context to provide further insight into the acquisition of the carbapenemase genes blaOXA-181 and blaNDM-5 of this successful lineage. From 127 whole genome sequenced isolates, we reconstructed an evolutionary framework of E. coli 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 E. coli ST131. B3/H24Rx appears to have evolved by the acquisition of the extended-spectrum ß-lactamase (ESBL)-encoding gene blaCTX-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 blaOXA-181 carbapenemase gene. Around 2014 the clade B4/H24RxC acquired a second carbapenemase gene, blaNDM-5, on a conserved IncFII plasmid. From an epidemiological investigation of 49 E. coli ST410 isolates from Danish patients, we identified five possible regional outbreaks, of which one outbreak involved nine patients with blaOXA-181- and blaNDM-5-carrying B4/H24RxC isolates. The accumulated multidrug resistance in E. coli ST410 over the past two decades, together with its proven potential of transmission between patients, poses a high risk in clinical settings, and thus E. coli ST410 should be considered a lineage with emerging 'high-risk' clones, which should be monitored closely in the future. Importance: Extra-intestinal pathogenic Escherichia coli (ExPEC) is the main cause of urinary tract infections and septicaemia. 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 E. coli 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 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.