Abstract
Escherichia coli 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 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 β-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 Extraintestinal pathogenic Escherichia coli (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 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 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.
Highlights
Introduction of blaOXA181 and blaNDM-5 into sequence type 410 (ST410)
We investigated the epidemiology of third-generation cephalosporin- and carbapenem-resistant ST410 E. coli isolates from Danish patients, to elucidate whether multidrug-resistant ST410 was causing national outbreaks or, alternatively, if a global clone was being introduced multiple times
E. coli ST410 genomes included in the study (49 genomes, collected from 46 patients from the national Danish surveillance program DANMAP, and 78 international genomes), including whole-genome sequencing (WGS)-based resistance gene profiling, subtyping by fimH allelic variation, and identification of plasmid replicons and plasmid multilocus sequence typing subtypes
Summary
The timing of introductions of blaOXA-181 and blaNDM-5 into B4/H24RxC was predicted using BEAST (Fig. 3). To investigate if blaOXA-181 was carried on an IncX3 plasmid, the genome scaffolds of the 63 ST410 genomes in B4/H24RxC with blaOXA-181 and/or IncX3 and an additional six genomes with blaOXA-181 and/or IncX3 were compared with the complete plasmid sequence of pAMA1167-OXA-181 from E. coli ST410 [10] (Fig. S8A). The results indicated that the plasmid harboring blaOXA-181 is well preserved; only one blaOXA-181positive ST410 isolate, from the United Kingdom, did not carry the IncX3 plasmid (the outermost ring, H14352020701). Two isolates from Denmark harbored the IncX3 backbone but did not carry the blaOXA-181 gene (CPO20150034 and CPO20170049)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
