Abstract
ABSTRACTEscherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131.
Highlights
Escherichia coli sequence type 131 (ST131) is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections
Escherichia coli sequence type 131 (ST131) is a recently emerged multidrug-resistant clone associated with urinary tract and bloodstream infections
Our comprehensive analysis of 95 E. coli ST131 genomes revealed that the virulence and mobile genetic element (MGE) profile was consistent with the phylogenetic structure of the ST131 lineage, with clade C strains sharing a generally conserved set of genes
Summary
Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Originally identified through its association with the CTXM-15 extended-spectrum -lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. IMPORTANCE Escherichia coli sequence type 131 (ST131) is a recently emerged and globally disseminated multidrug-resistant clone frequently associated with human urinary tract and bloodstream infections. A large study of methicillinresistant Staphylococcus aureus (MRSA) was able to date the emergence of an FQR clade to the mid-1980s [20] These studies motivated us to combine data sets from our geographically diverse previous study [2] and from the temporally diverse study by Price et al [5] to investigate the evolution of ST131 with the highest possible resolution
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