A Culture-Independent Sequence-Based Metagenomics Approach to the Investigation of an Outbreak of Shiga-Toxigenic Escherichia coli O104:H4

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Abstract
The outbreak of Shiga-toxigenic Escherichia coli (STEC), which struck Germany in May-June 2011, illustrated the effects of a bacterial epidemic on a wealthy, modern, industrialized society, with more than 3000 cases and more than 50 deaths.1 During an outbreak, rapid and accurate pathogen identification and characterization is essential for the management of individual cases and of an entire outbreak. Traditionally, clinical bacteriology has relied primarily on laboratory isolation of bacteria in pure culture as a prerequisite to identification and characterization of an outbreak strain. Often, however, in vitro culture proves slow, difficult, or even impossible, and recognition of an outbreak strain can be difficult if it does not belong to a known variety or species for which specific laboratory tests and diagnostic criteria already exist. For example, during the German outbreak, infection was caused by an unusual serotype (STEC O104:H4) that had not previously been seen in the context of epidemic disease and could not be detected easily with the standard microbiological methods in use at the start of the outbreak for diagnosing STEC infection.