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.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Bacteremia drug therapy   microbiology   MeSH
• beta-Lactamases genetics   MeSH
• Biofilms drug effects   MeSH
• Escherichia coli drug effects   genetics   MeSH
• Virulence Factors genetics   MeSH
• Genomics methods   MeSH
• Urinary Tract Infections drug therapy   microbiology   MeSH
• Escherichia coli Infections drug therapy   microbiology   MeSH
• Chickens microbiology   MeSH
• Humans MeSH
• Drug Resistance, Multiple, Bacterial genetics   MeSH
• Multilocus Sequence Typing methods   MeSH
• Plasmids genetics   MeSH
• Whole Genome Sequencing methods   MeSH
• Virulence genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH