Metagenomics used to identify organisms in outbreaks of serious infectious disease
Researchers have been able to reconstruct the genome sequence of an outbreak strain of Shiga-toxigenic Escherichia coli (STEC), which caused over 50 deaths in Germany, using an approach known as metagenomics which bypasses the need for growing bacteria in the lab.
An international team coordinated by Mark Pallen, Professor of Microbial Genomics at Warwick Medical School, was able to reconstruct the genome sequence through the direct sequencing of DNA extracted from microbiologically complex samples. The study, published in a genomics-themed issue of JAMA on 10 April, highlights the potential of this approach to identify and characterise bacterial pathogens directly from clinical specimens.
Metagenomics has been used previously in a clinical diagnostic setting to identify the cause of outbreaks of viral infection, but this is its first reported use in an outbreak of bacterial infection.
Professor Pallen explained the significance of the STEC outbreak, “The outbreak of Shiga-toxigenic Escherichia coli illustrated the effects of a bacterial epidemic on a wealthy, modern, industrialized society, with more than 3,000 cases and more than 50 deaths reported in Germany between May and June of 2011.”
He added, “During an outbreak such as this, rapid and accurate pathogen identification and characterisation is essential for the management of individual cases and the outbreak as a whole. Traditionally, clinical bacteriology has relied primarily on laboratory isolation of bacteria in pure culture to identify and characterise an outbreak strain."
Oftentimes the process of laboratory culture proves slow and the recognition of an outbreak strain can be difficult if it belongs to an unknown variety or species for which specific laboratory tests and diagnostic criteria don’t already exist.
Professor Pallen summarised what this means for the idenification of future outbreaks,
There are numerous drawbacks to the use of nineteenth-century approaches such as microscopy and culture when it comes to classification. Our results illustrate the potential of metagenomics as an open-ended, culture-independent approach for the identification and characterization of bacterial pathogens during an outbreak. There are challenges, of course, including speeding up and simplifying workflows, reducing costs and improving diagnostic sensitivity. However, given the dizzying pace of progress in high-throughput sequencing, these are not likely to remain problems for very long.
Professor Pallen led the team, which included two other recently appointed Warwick microbiologists, Chrystala Constantinidou and Jacqueline Chan, together with scientists from the University of Birmingham, the University of Glasgow, the University Medical Centre Hamburg-Eppendorf in Germany and the sequencing company Illumina, to develop and exploit novel sequencing and analytic approaches.
JAMA. 2013;309(14):1502-1510; http://jama.jamanetwork.com/article.aspx?articleid=1677374