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
• antibakteriální látky farmakologie   MeSH
• bakteriemie farmakoterapie   mikrobiologie   MeSH
• beta-laktamasy genetika   MeSH
• biofilmy účinky léků   MeSH
• Escherichia coli účinky léků   genetika   MeSH
• faktory virulence genetika   MeSH
• genomika metody   MeSH
• infekce močového ústrojí farmakoterapie   mikrobiologie   MeSH
• infekce vyvolané Escherichia coli farmakoterapie   mikrobiologie   MeSH
• kur domácí mikrobiologie   MeSH
• lidé MeSH
• mnohočetná bakteriální léková rezistence genetika   MeSH
• multilokusová sekvenční typizace metody   MeSH
• plazmidy genetika   MeSH
• sekvenování celého genomu metody   MeSH
• virulence genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.

• MeSH
• antibiotická rezistence genetika   MeSH
• Escherichia coli genetika   patogenita   MeSH
• fylogeneze MeSH
• genom bakteriální účinky léků   MeSH
• infekce vyvolané Escherichia coli farmakoterapie   genetika   MeSH
• lidé MeSH
• molekulární evoluce * MeSH
• regulační oblasti nukleových kyselin genetika   MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH