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Fighting Outbreaks with Genomics

This summer, Germany was ravaged by an E. coli outbreak that sickened 3,500 people and killed 50. Several research groups around the world quickly mobilized their labs to sequence the bug's genome and analyze it, identifying effective treatment options within days. The University of Maryland School of Medicine's David Rasko was one of the American researchers who teamed up with a group from Denmark's Staten Serums Institut to sequence the bacterium and investigate the epidemiology of the outbreak. At the annual meeting of the Association for Molecular Pathology held in Grapevine, Texas, this week, Rasko spoke about his experience, saying whole-genome sequencing has a place in the rapid response to disease outbreaks.

Researchers from BGI, the University of Gottingen in Germany, the USA/Denmark team, and others all used different technologies to sequence the bacterium, and each had its own advantages, Rasko said. Using Life Technologies' Ion Torrent Personal Genome Machine, researchers in Germany and China were able to sequence the strain in three hours and develop a diagnostic test for the infection within five days. The team then released the raw data, which many researchers analyzed, Rasko said.

Rasko's team used Pacific Biosciences' technology to sequence the bacterium. Although PacBio's machine took slightly longer, Rasko said his group used it to generate longer reads. Between all of these technologies and the rapid analysis done by experts, the teams were able to compare the genome of this outbreak strain to other E. coli strains, build a phylogeny, and determine that this strain, O104:H4, had never been seen before, and carried a Shiga toxin.

Functional genomics analysis told the researchers that administering ciprofloxacin, as is commonly done with bacterial infections, would make sick patients fare worse because of the Shiga toxin, Rasko said. And comparative genomics analysis showed the researchers that a plasmid present in the outbreak strain conferred upon it genes responsible for antibiotic resistance. All this, he said, shows that whole-genome sequencing and subsequent genomic analysis can be used to help doctors deal with outbreaks in a timely, thorough, and efficient manner.

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