Whole Genome Sequencing

Whole genome sequencing (WGS) or next-generation sequencing is an emerging technology that allows scientists to map the genetic sequence of pathogens and other organisms with such precision that they can distinguish between different strains of a bacterium and even slight variations by geography within the same strain. As the cost of gene sequencing equipment continues to decline, FDA and state public health laboratories will increasingly use WGS to investigate outbreaks of foodborne illnesses. They will store the sequenced genomic information in large databases, which will be publicly accessible nationally and internationally.

But FDA will employ WGS not only during outbreaks; the agency announced it will also use WGS to analyze samples from food companies taken during routine inspections in order to monitor compliance with the Food Safety Modernization Act (FSMA) and other regulations. Thus, WGS may become a two-edged sword—one that can quickly pinpoint the source of an outbreak, preventing illness and potentially saving lives, but also a dagger pointed at the hearts of food companies when no outbreak has occurred.

For years, pathogen testing and bacterial subtyping has been performed using pulsed-field gel electrophoresis (PFGE), an older and less sensitive technology. Among other limitations, PFGE cannot differentiate certain strains of Salmonella or distinguish between samples of isolates associated with previous contaminations. WGS, on the other hand, is far more reliable and sensitive. By pairing a pathogen’s genomic information with geographic information systems, a mapping technology, and applying the principles of evolutionary biology, investigators can identify the root source of contamination—a powerful tool given the rise of food products containing ingredients imported from different countries.

“What genome sequencing allows us to do with food traceback is unprecedented,” says Eric Brown, PhD, director of FDA’s Division of Microbiology. “It’s like upgrading from an old backyard telescope to the Hubble.” PFGE has begun to show its age, adds Brian Sauders, PhD, a senior food bacteriologist at the New York State Department of Agriculture & Markets. “PFGE is like looking at a globe of the Earth with only seven labeled continents, while WGS provides better than Google Earth map resolution of the entire world surface complete with names of many key and detailed features and a searchable database with zoom-to-point of reference capabilities,” Dr. Sauders wrote in an Association of Public Health Laboratories blog post.

Solving Outbreaks

The U.S. FDA and the CDC used WGS to help solve two widely publicized multistate outbreaks in 2014. The first involved an outbreak of Listeria monocytogenes. Reports of listeriosis had been reported as early as August 2013. Investigators first used PFGE to identify cases that may have been part of the outbreak using data archived in PulseNet, a network run by the CDC that connects public health and food regulatory agency laboratories performing molecular surveillance of foodborne infections. After the Listeria strain had been isolated from patients, investigators used WGS to definitively link it to Hispanic-style cheese produced by Roos Foods of Kenton, Del. In early 2014, Roos issued a recall and FDA suspended its facility registration.

“This was the first time we used whole genome sequencing to match the environmental and food samples with the CDC’s human biological samples and it helped support the agency in taking regulatory action,” says Dr. Brown. “We were able to suspend food production at a facility to minimize an outbreak.”

FDA also used WGS to identify a multi-state outbreak strain of Salmonella Braenderup and link it to almond and peanut butter manufactured by nSpired Natural Foods Inc. in Ashland, Wash. Recalled brands included Arrowhead Mills, MaraNatha, Trader Joe’s, Whole Foods, Safeway, and Kroger. In both cases, FDA inspectors had collected pathogen samples during routine inspections of production facilities; in the case of Roos Foods, they also had collected samples from finished food products.