RT Journal Article SR Electronic T1 Evolutionary history of the global emergence of the Escherichia coli epidemic clone ST131 JF bioRxiv FD Cold Spring Harbor Laboratory SP 030668 DO 10.1101/030668 A1 Nicole Stoesser A1 Anna E. Sheppard A1 Louise Pankhurst A1 Nicola de Maio A1 Catrin E. Moore A1 Robert Sebra A1 Paul Turner A1 Luke W. Anson A1 Andrew Kasarskis A1 Elizabeth M. Batty A1 Veronica Kos A1 Daniel J. Wilson A1 Rattanaphone Phetsouvanh A1 David Wyllie A1 Evgeni Sokurenko A1 Amee R. Manges A1 Timothy J. Johnson A1 Lance B. Price A1 Timothy E. A. Peto A1 James R. Johnson A1 Xavier Didelot A1 A. Sarah Walker A1 Derrick W. Crook A1 Modernising Medical Microbiology Informatics Group (MMMIG) YR 2015 UL http://biorxiv.org/content/early/2015/11/06/030668.abstract AB Background Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined.Results This study of the largest worldwide collection (n = 215) of sequenced ST131 E. coli isolates to date demonstrates that clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of a blaCTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids, and chromosomal integration of blaCTX-M within sub-clusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed amongst ST131, the blaCTX-M-14/14-like group.Conclusions The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli. These data also highlight the global imperative to reduce specific antibiotic selection pressures, and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages.