International audienceThe degree to which molecular epidemiology reveals informationabout the sources and transmission patterns of an outbreakdepends on the resolution of the technology used and the samplesstudied. Isolates of Escherichia coli O104:H4 from the outbreak centeredin Germany in May–July 2011, and the much smaller outbreakin southwest France in June 2011, were indistinguishable by standardtests. We report a molecular epidemiological analysis usingmultiplatform whole-genome sequencing and analysis of multipleisolates from the German and French outbreaks. Isolates from theGerman outbreak showed remarkably little diversity, with onlytwo single nucleotide polymorphisms (SNPs) found in isolates fromfour individuals. Surprisingly, we found much greater diversity (19SNPs) in isolates from seven individuals infected in the French outbreak.The German isolates form a clade within the more diverseFrench outbreak strains. Moreover, five isolates derived from a singleinfected individual from the French outbreak had extremelylimited diversity. The striking difference in diversity between theGerman and French outbreak samples is consistent with severalhypotheses, including a bottleneck that purged diversity in theGerman isolates, variation in mutation rates in the two E. coli outbreakpopulations, or uneven distribution of diversity in the seedpopulations that led to each outbreak

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