Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Evolution and global dissemination of the multidrug resistant Escherichia coli ST131 clone (#191)

Nouri Ben Zakour 1 , Areej Alsheikh-Hussain 1 , Nhu TK Nguyen 1 , Melinda Ashcroft 1 , Leah Roberts 1 , Brian Forde 1 , Mitchell Stanton-Cook 1 , Mark A Schembri 2 , Scott A Beatson 1
  1. Australian Centre for Ecogenomics & School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
  2. School of Chemistry and Molecular Biosciences & Australian Infectious Diseases Centre, The University of Queensland, St Lucia, Australia

Escherichia coli sequence type 131 (ST131) is predominantly associated with urinary tract and bloodstream infections, and was first reported in the United Kingdom in 2008. Since then, it has rapidly disseminated worldwide to become the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone. E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolone, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele and the production of the CTX-M-15 extended-spectrum beta-lactamase. Yet, the sequence of events leading to the rapid emergence and successful spread of this multi-drug resistant clone remains largely undetermined, mainly due to the lack of geographical and temporal diversity of strain collections studied so far.

In order to reconstruct the evolutionary scenario of the emergence of FQR E. coli ST131, we combined publically available genomic data of 188 ST131 strains, spanning the years 1967 to 2011 and from 9 geographical regions. We investigated the ST131 clonal structure and identified the genetic changes that define the global phylogeny of E. coli ST131. Contrary to some initial reports, we confirmed the defining role that recombination has played in shaping the evolution of the distinct lineages. Thanks to the increased temporal resolution achieved by our combined dataset, divergence time estimation using Bayesian Evolutionary Analysis by Sampling Trees (BEAST) could be performed and revealed that the multidrug resistant ST131 lineage originated around 1987, coincidently following the first clinical usage of fluoroquinolone in 1986. Geographical ancestral reconstruction also suggested that FQR ST131 most likely emerged in North America before spreading globally. Finally, we were able to identify key strains harboring intermediate states leading to more resistant lineages. Taken altogether, we propose that following the progressive acquisition of mobile genetic elements and recombination events, which likely increased the virulence and fitness of ST131, point mutations conferring resistance to fluoroquinolone were the pivotal events leading to a rapid population expansion in 1990’s to early 2000’s.

This work highlights the challenges and rewards of combining publicly available genomic datasets and how this approach can synergistically provide better resolution into the series of events leading to the emergence of highly successful multi-drug resistant bacteria.