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  1. Whole Genome Sequencing (WGS) Program

Proactive Applications of Whole Genome Sequencing Technology

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Although public health officials sequence foodborne pathogens after a foodborne illness outbreak or event has occurred, that isn’t the only time they are sequenced and the genomic information sequencing provides can be used for more than just determining the scope of outbreaks and speeding traceback investigations. It can be used: as an industry tool for monitoring ingredient supplies, the effectiveness of preventive and sanitary controls, and to develop new rapid method and culture independent tests; to determine the persistence of pathogens in the environment; to monitor emerging pathogens; and as a possible indicator of antimicrobial resistance.

Below you will find more information about these proactive applications of whole genome sequencing technology.

To Provide Benefits to the Food Industry

The benefits that come from leveraging the information whole genome sequencing provides aren’t just limited to public health officials. Members of the food industry and diagnostic test developers can use it as well.

FDA regulated food manufacturers are required to ensure that their products are safe for consumption. Part of meeting this requirement is making sure that the ingredients they use are free from bacterial pathogens and if a bacterial pathogen is present, that the processing of the food include steps that are sufficient to kill the pathogen. Accordingly many food companies periodically test ingredients received from their suppliers as additional verification of the ingredients’ safety. Similarly, companies may conduct environmental sampling in their processing plants to verify the effectiveness of their processing and sanitation controls. By conducting whole genome sequencing on any bacteria isolated from their sampling efforts companies will have detailed information about the pathogen(s) detected. They can then compare this to the genomic information publicly available in GenomeTrakr. In the case of an incoming ingredient, it may reveal information about the route source of the ingredient contamination in their supply chain. It may also identify which preventive or sanitary controls may have failed and need to be corrected.

The genomic information in the publicly accessible GenomeTrakr database can also be drawn on by the food industry, researchers, and instrument makers to develop rapid method and culture independent tests that can be utilized for screening for known pathogen strains.

To Evaluate Persistence of Pathogens in the Environment

Since the late 1990s there have been recurring outbreaks of salmonellosis linked to tomatoes grown on the eastern shores of the mid-Atlantic states. What is unclear is how the tomatoes became contaminated with Salmonella. To better understand what might be happening, in 2009 FDA began to examine the persistence of pathogens in the running and standing surface water found near high water input horticultural commodity growing areas in the mid-Atlantic states. It did this by collecting environmental samples from the water itself and from the land immediately adjacent to it. When pathogens were detected they were sequenced and the genomic information and corresponding geographic information were recorded for comparison to future samples. (This information is now stored in the GenomeTrakr database at NCBI.)

This effort has already yielded valuable information. In 2010 there was an outbreak of Salmonella Newport infections reported by patrons of certain Washington, DC restaurants. Whole genome sequencing of the clinical isolates showed the strain was a very close match to a strain found in a pond on the eastern shore that was adjacent to a tomato growing area. Investigators were then able to match the shipping records from tomatoes grown in that field to the restaurant chains. While whole genome sequencing helped identify the commodity linked to the outbreak and its source, having a database of genomic information for environmental samples offers another long term benefit. It will help us to better understand how pathogens spread within and between geographic areas, and what conditions or growing practices might influence whether or not a pathogen will make its way into a nearby growing area. With this information improved controls to prevent foodborne illness can be implemented on the farm.

To Monitor Emerging Pathogens

There are public health benefits that can be achieved by knowing the genomic makeup of foodborne pathogens that are known to be harmful to humans. But there are also benefits to knowing the genetic makeup of foodborne bacteria that are either 1) known to be pathogenic to animals, but not known to be pathogenic to humans, or 2) not known to be pathogenic at all. Why? Because sometimes pathogenicity arises from mutations to non-pathogenic bacteria or from horizontal gene transfer between bacteria. In essence a non-pathogenic strain of bacteria evolves into a pathogenic strain over a period of time. If the non-pathogenic foodborne bacteria can be sequenced and the genomic and corresponding geographic information for the sample are stored in a searchable database, it may provide faster traceback capability than if the historically benign bacteria had never been sequenced. Even though there might not be a match for the newly recognized pathogenic strain, it may be possible to determine the lineage from which the pathogenic strain evolved. This determination may aid in the identification of the food or ingredient that could be responsible for causing the foodborne illness, and may also contribute to understanding the environmental conditions under which the genetic changes occurred.

In an effort to monitor emerging pathogens and to determine the lineage from which bacterial pathogens evolve, FDA is sequencing all pathogens collected from food and environmental samples and uploading them to the publicly searchable GenomeTrakr database.

As a Possible Indicator of Antimicrobial Resistance

FDA’s National Antimicrobial Resistance Monitoring System (NARMS), is a collaboration with CDC and USDA to monitor antibiotic resistance in foodborne bacteria. NARMS laboratories are conducting studies using whole genome sequencing to determine if the presence of certain genes in Salmonella and Campylobacter can be used to predict the pathogens’ resistance to antibiotics. So far the research by NARMS, and by others, shows a high degree of correlation between clinical antibiotic resistance and the presence of known resistance genes. However, additional research is needed before information from whole genome sequencing could be used to help select appropriate antibiotics for treating patients. In the meantime, sequence data generated from NARMS can be used by the FDA to understand the dissemination of antibiotic resistance bacteria and their genes via foods. These data can also help to improve the process of assessing risks associated with different antibiotic use practices. This could allow for a more targeted approach to their use that could help preserve an antibiotic’s effectiveness and safety when given to people or animals.

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