The Genomic Era Is Here

“People like to focus on the technology as the paradigm shift but, in my opinion, a really important advance is the open data-sharing model,” exclaims Ruth Timme, PhD, FDA senior scientist and GenomeTrakr network principal coordinator. Of course, this approach would not prevent some aspects of the metadata to be held by individual organizations because of concerns about public release of proprietary information. The open database also allows FDA to go beyond the development of a source-tracking scheme. Several additional applications and benefits of the technology include: readily available antimicrobial resistance profiling to 98 percent accuracy; serological characterization without a need for classical antibody testing; virulence pathogenicity assessment for emerging bacterial pathogens; and, of course, high resolution subtyping, which has been its most widespread application to date.

“WGS is good because it can dig down deeper and identify the specific isolate and tell investigators what area or producer it could have come from,” says Capt. Palmer Orlandi, PhD, senior science advisor in FDA’s Office of Foods and Veterinary Medicine and member of the Commissioned Corps of the U.S. Public Health Service. Sample collection and sequence cataloging from food production sites can help monitor compliance with FDA’s rules on safe food handling practices and enhance preventive controls for food safety.

Ultimately, sequencing capability should be distributed to as many sites as possible so that public health laboratories can move sequences from their collections and current surveillance and inspection activities into the database as quickly as possible. Dr. Allard emphasizes that “this public approach provides useful data to industry and academic partners, as well as to any federal or international agency that wishes to add value to the collected data.” The current GenomeTrakr database contains sequences from roughly 14,000 Salmonella isolates and more than 3,300 Listeria isolates, and is growing by more than 700 new draft genomes per month. New phylogenetic trees showing emerging linkages and relatedness are produced daily by NCBI and are publicly accessible.

Casting a Broad Net

The GenomeTrakr has already expanded and benefitted from other important WGS projects being carried out by public health experts in the U.S. and abroad. The CDC’s Real-Time Listeria monocytogenes WGS pilot, which is sequencing all clinical cases of L. monocytogenes reported by the states since the fall of 2013 to enhance surveillance, is an example. FDA and other GenomeTrakr sites are working with CDC by contributing genomes of all food and environmental L. monocytogenes to the database. The work is making great strides in public health officials’ efforts to delimit illness clusters and sources of contamination caused by this dangerous pathogen.

Errol Strain, PhD, CFSAN’s lead bioinformaticist, puts a finer point on the importance of the collaboration with CDC. “To be able to go beyond what we once thought was a typical Listeria outbreak and now detect the outlying and more subtle contamination events caused by this pathogen is hugely impactful to food safety and public health.” This real time collaboration has increased the number of Listeria outbreaks discovered and characterized, and has reduced the time to detection and increased regulatory activity for this pathogen in a significant way.

While tracking and tracing foodborne outbreaks is a primary application of the GenomeTrakr network, it is essential to note the broad important uses of such a database to food safety stakeholders. For instance, academic and environmental microbiology partners are using the database to accumulate broad amounts of genomic information on enteric pathogens that thrive in and around agricultural environments. Technology partners are mining these data for novel genetic targets to incorporate into assay design for improved pathogen detection systems, and industry partners are using the technology to mitigate safe food production and processing systems. Effective monitoring of supply chain ingredients means downstream cost and material savings for industry if they catch problems earlier and understand the root cause of the contamination event so that they can fix the problem and prevent it from happening in the future. Moreover, being able to distinguish between resident, facility contaminations versus a reintroduction of a pathogen strain from raw materials is a hugely beneficial application of the technology as the preventative solutions are different depending on where the contamination is coming from. Finally, the cost savings potential through monitoring with high certainty and with multi-analytes in one test cannot be overstated.

What’s Next

Through numerous earlier case studies gathered from 2009 to the present and now weekly regulatory decision making, it is clear that WGS is validated and reproducible. Moreover, WGS will be adopted globally as the new method for foodborne pathogen surveillance and characterization. To be universal and comprehensive, more states and countries need to be added to the database and there needs to be a harmonization of the different networks being built both nationally and internationally. More work still is needed for successful implementation of a global food shield including: increased funding for instrumentation and training; issues surrounding data and metadata release into the public domain; harmonization among different authorities with sometimes distinct mandates and conflicting missions; and finally issues regarding validating alternative informatics approaches to interpreting the data. None of these barriers are insurmountable, and many believe it is only a matter of time until we will see a global food shield.

In Closing

The years 2014 and 2015 are watershed years for the use of WGS for food safety and public health in that many firsts were encountered as WGS left the research arena and entered into regular production and use across many state, federal, and international food safety agencies. Numerous successful applications of pathogen surveillance and characterization among academic, industry, and government partners has made WGS more prominent than ever and it has never been more apparent that the future lies with this technology. One can expect additional applications and greater impact as more partners join these efforts. These initial investments into the GenomeTrakr network, the new WGS technologies, and the hard work of many public health professionals are truly transforming the public health paradigm and these improvements will have long lasting benefits for the public and food safety.