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Whole-Genome Sequencing Expected to Revolutionize Outbreak Investigations

For decades, food safety experts have lived with the reality that roughly one-third of foodborne illness outbreak investigations ended without finding the source.

But with the wide proliferation of new laboratory technology on the horizon, outbreak investigations could soon become more accurate, more efficient and more complete, according to researchers at Cornell University, the New York State Department of Health and the U.S. Food and Drug Administration.

The new technology is known as rapid whole-genome sequencing, a process of analyzing the complete DNA sequence of organisms, included foodborne pathogens such as Salmonella and E. coli. It’s the same technology used to generate the human genome, but in epidemiology, the process grants investigators the ability to much more precisely identify organisms causing outbreaks, right down to their DNA.

Older forms of bacterial subtyping, such as pulsed-field gel electrophoresis (PFGE), are still important for the detection and investigation of outbreaks, but they lack the level of detail needed for outbreak detection. In other words, it’s been impossible until the advent of genome sequencing to truly know whether two people infected with the same strain of pathogen were genuinely sickened by the same food source.

By letting investigators identify a bacterium down to the DNA, genome sequencing allows much more certainty when matching clusters of illnesses and narrowing down the list of potential food sources. For example, two people in the same area might both be sick with Salmonella Heidelberg from two different sources, but investigators could only know that the illnesses were unrelated by looking at the bacteria’s DNA.

The technology has been in use at a select number of laboratories around the country for a little more than a year now. Earlier this year, a deadly outbreak of Listeria in Maryland was traced back to Delaware-based dairy manufacturer Roos Foods through genome sequencing. Health officials were then able to shut the facility down.

“What genome sequencing allows us to do with food traceback is unprecedented. It’s like upgrading from an old backyard telescope to the Hubble,” said Dr. Eric Brown, director of the Division of Microbiology at FDA’s Office of Regulatory Science.

Brown and FDA colleagues recently collaborated with researchers from Cornell University and the New York State Department of Health to demonstrate the feasibility of using whole-genome sequencing to investigate foodborne illness outbreaks in a state health laboratory.

Their study, published in the August 2014 edition of Emerging Infectious Diseases, consisted of two parts. The first was an analysis of bacterial samples from a known Salmonella outbreak occurring in 2010. Using whole-genome sequencing, the researchers were able to attribute additional cases to the outbreak that were not — and could not have been — attributed when the original investigators relied on PFGE.

The second part of the study involved the real-time use of genome sequencing in conjunction with PFGE technology to analyze incoming Salmonella cases in 2012. In that test, genome sequencing found more cases connected to an outbreak than could be determined using PFGE.

The conclusion: Whole-genome sequencing “vastly improved” the detection of outbreak cases and the amount of detail available to investigators.

“Using PFGE, we couldn’t find much meaningful differences between strains. But by using whole-genome sequencing, we can establish much better relationships between bacteria in the population,” said Dr. Henk den Bakker, research associate at Cornell’s Department of Food Science and lead author of the study.

As whole-genome sequencing becomes more widespread, there will be less reason to use PFGE, den Bakker added.

Until recently, whole-genome sequencing technology was simply too costly for most public health laboratories to use, although the technology is quickly becoming more cost-effective. Part of that cost is due to labs needing someone on staff who can translate the genetic information into information epidemiologists can use in their investigations.

Right now, the field of epidemiology is entering a transition period where genome sequencing is replacing PFGE. A vast amount of historic PFGE data exist on outbreak networks, however, and epidemiologists are now working to sequence historic pathogenic samples to enhance new whole-genome databases.

One such database is FDA’s Genome Trakr Network, a pilot database for state and federal laboratories to collect and share genomic data on foodborne pathogens. The network currently consists of seven state health department labs and 10 FDA field labs, according to FDA.

“It’s clear that we’re going to be adopting and expanding genome sequencing to many more state labs. State labs are the boots on the ground,” said Dr. Marc Allard, research area coordinator for genomics for the Division of Microbiology at FDA’s Office of Regulatory Science.

Beyond the states, the Genome Trakr database will network with international databases under the umbrella of the Global Microbial Identifier. In the future, every new outbreak sample will be compared with global records to track the sources of outbreaks and determine when or where new pathogens are emerging.

And, ultimately, the researchers say it should lead to a system that prevents more illnesses worldwide by tracking down the sources faster and more accurately.

“What’s the cost of not finding the food source?” Allard asked. “More people getting sick and potentially dying, along with larger recalls and more litigation. [Whole-genome sequencing] will have a such a broad impact on public health that it’s difficult to estimate.”

© Food Safety News
  • oldcowvet

    Only”something’? My pathologist friends liked to joke it was job security for the microbiologists.

  • Carl Custer

    Bacteria are different from eucaryotes. Thus, they are biota, not flora or fauna. Here is a short article that appeared in Microbe in 2010:
    The Phylogenomic Species Concept for Bacteria and Archaea
    James T. Staley
    http://www.microbemagazine.org/index.php?option=com_content&view=article&id=539:the-phylogenomic-species-concept-for-bacteria-and-archaea&Itemid=254
    Summary
    • A phylogenomic species concept that relies on phylogenetic and genomic approaches for circumscribing species is proposed.
    • Although phylogenetic analyses of 16S rRNA sequences are currently used to ascertain the taxonomy of Bacteria and Archaea at higher taxonomic levels, less highly conserved genes must be used for species.
    • Current applications of the phylogenomic species concept, such as multiple-locus sequence analysis, are already being used to identify clades that can be classified as species.
    • Horizontal gene transfers pose a major challenge for any taxonomy, but genomic approaches will help resolve this issue.
    • The phylogenomic species concept could apply universally to all organisms.

    Bacteriologists have not yet adopted a concept for a species. Bacterial and archaeal species are defined on the basis of phenotypic properties and whole-genome DNA-DNA hybridization. Each species must have unique phenotypic properties and exhibit more than 70% DNA hybridization among strains. This combination of phenotype and genotype, sometimes referred to as the polyphasic species definition, was a breakthrough in bacterial taxonomy and has served microbiologists very well by stabilizing the field and bringing uniformity to classifying species of Bacteria and Archaea.