Genomic and Functional analysis of emerging virulent and multidrug-resistant Escherichia coli lineage sequence type 648.

Research output: Contribution to journalArticle


  • Katharina Schaufler
  • Torsten Semmler
  • Lothar H. Wieler
  • Darren J. Trott
  • Johann Pitout
  • Gisele Peirano
  • Jonas Bonnedahl
  • Monika Dolejska
  • Ivan Literak
  • Stephan Fuchs
  • Niyaz Ahmed
  • Mirjam Grobbel
  • Carmen Torres
  • Derek Pickard
  • Christa Ewers
  • Nicholas J Croucher
  • Jukka Corander
  • Sebastian Guenther

Colleges, School and Institutes

External organisations

  • University of Cambridge
  • Imperial College London
  • Institute of Pharmacy, University of Greifswald
  • Robert Koch Institute
  • The University of Adelaide
  • Calgary Laboratory Services
  • University of Calgary
  • Linköping University
  • Kalmar County Council
  • University of Veterinary and Pharmaceutical Sciences Brno
  • International Center for Diarrheal Disease Research, Bangladesh
  • German Federal Institute for Risk Assessment (BfR)
  • Universidad de La Rioja
  • Justus Liebig University Giessen
  • Wellcome Trust Sanger Institute
  • Institute of Microbiology and Epizootics, Freie Universität Berlin


The pathogenic extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli lineage ST648 is increasingly reported from multiple origins. Our study of a large and global ST648 collection from various hosts (87 whole-genome sequences) combining core and accessory genomics with functional analyses and in vivo experiments suggests that ST648 is a nascent and generalist lineage, lacking clear phylogeographic and host association signals. By including large numbers of ST131 ( n  = 107) and ST10 ( n  = 96) strains for comparative genomics and phenotypic analysis, we demonstrate that the combination of multidrug resistance and high-level virulence are the hallmarks of ST648, similar to international high-risk clonal lineage ST131. Specifically, our in silico, in vitro, and in vivo results demonstrate that ST648 is well equipped with biofilm-associated features, while ST131 shows sophisticated signatures indicative of adaption to urinary tract infection, potentially conveying individual ecological niche adaptation. In addition, we used a recently developed NFDS (negative frequency-dependent selection) population model suggesting that ST648 will increase significantly in frequency as a cause of bacteremia within the next few years. Also, ESBL plasmids impacting biofilm formation aided in shaping and maintaining ST648 strains to successfully emerge worldwide across different ecologies. Our study contributes to understanding what factors drive the evolution and spread of emerging international high-risk clonal lineages.

Bibliographic note

Copyright © 2019 American Society for Microbiology.


Original languageEnglish
Article numbere00243-19
JournalAntimicrobial Agents and Chemotherapy
Issue number6
Early online date18 Mar 2019
Publication statusPublished - 18 Jun 2019


  • Biofilm formation, ESBL-producing clonal lineages, MDR, NFDS modeling, Phylogenetics, ST648, Virulence