Tackling drug resistant infection outbreaks of global pandemic Escherichia coli ST131 using evolutionary and epidemiological genomics
Tim Downing
(Submitted on 4 Nov 2014)

High-throughput molecular approaches are required to investigate the origin and diffusion of antimicrobial resistance in rapidly radiating pathogen outbreaks. The most frequent cause of human infection is Escherichia coli, which is dominated by ST131, a single pandemic clone. This epidemic subtype possesses an extensive array of virulence elements and tolerates many drugs. Frequent global sweeps of new dominant ST131 varieties necessitate deep genomic scrutiny of their spread, evolution and lateral transfer of drug resistance genes. Phylogenetic methods that decipher past events can predict future patterns of virulence and transmission based on genetic signatures of adaptation and recombination. Antibiotic tolerance is controlled by natural variation in gene expression levels, which can initiate delayed cell growth. This dormancy allows survival despite drug exposure, and yet may only be present in part of the infecting cell population. Consequently, genomic epidemiology needs to explore the scale of phenotypic regulatory control acting on RNA. A multi-faceted approach can comprehensively assess antimicrobial resistance in E. coli ST131 in terms of within-host genetic heterogeneity, regulation of gene expression, and transmission dynamics between hosts to achieve a goal of pre-empting resistance before it emerges by optimising drug treatment protocols.