The US Centers for Disease Control and Prevention (CDC) estimates that each year roughly one in six Americans (or 48 million people) become ill, 128,000 are hospitalised and 3,000 die of food-borne diseases. But with the increasing amount of food trade between cities, countries and continents, it is extremely difficult for even the most experienced scientists to determine the precise source of these outbreaks.

"The 100K Genome Project, which is expected to be completed within five years, will use the most-up-to-date genomic sequencing techniques."

The situation is made still more challenging because of the lack of genomic information about the top outbreak-causing pathogens, such as Salmonella, Campylobacter, E. coli and Listeria, which are able to adapt in food, the environment and animals, and thereforeconsequently evade identification.

But work is now underway, in the form of the 100K Genome Project, to help speed identification of the bacteria responsible for food-borne outbreaks.

Led by Dr Bart Weimer, a professor in the department of population health and reproduction at the UC Davis School of Veterinary Medicine, and conceived in collaboration with Agilent Technologies, the US Food and Drug Administration (FDA) and the CDC, the ambitious project aims to sequence the genomes of 100,000 infectious micro-organisms and make this information available in a free, public database.

"It’s becoming clear that the molecular biomarkers we’re using in the molecular testing for food pathogens are not as robust as we need them to be; it’s being limited by the lack of genome sequences available for pathogens," Weimer said.

"Independently, the FDA and my laboratory were working with Agilent Technologies to do something about this, and we both came to the conclusion that we needed more genomes. So we decided to link up and combine networks to go after this huge number of genomes that everyone can share."

Need for speed: next generation sequencing reduces identification times

The 100K Genome Project, which is expected to be completed within five years, will use the most-up-to-date genomic sequencing techniques (next generation sequencing or NGS) to create the database.

"The situation is made still more challenging because of the lack of genomic information about the top outbreak-causing pathogens."

And open access to this comprehensive library of food-borne pathogen genomes will allow researchers to develop tests that can identify the type of bacteria present in a sample within a matter of days or hours, significantly faster than the approximately one week it now takes between diagnosis and genetic analysis.

"It could impact society hugely," Weimer emphasised. "You’d have the information to control outbreaks much, much faster."

The need for this sort of approach was recently highlighted by the E. coli 0104 outbreaks in Europe, where genetic exchange led to a chimeric genome (a combination of two different types of organism) that was far more pathogenic than either of the other two organisms on its own.

According to Weimer, without next generation sequencing, the cause of the outbreak would have been almost impossible to pin down. "They didn’t know what they were hunting for," he explained. "They were looking for two different types of organism, not realising that they had recombined and created a brand new organism."

Back to the source: outbreak origins

""There are ‘forensic footprints’ you can identify to determine which region a particular isolate came from.""

Yet, the creation of this pathogen database is only part of the public response to the global issue of food-borne outbreaks. While the new genome library will significantly speed the testing of raw ingredients, finished products and environmental samples taken during the investigation of outbreaks, it needs to be used as part of an overall surveillance and outbreak investigation system.

So, for example, food safety officials need to be able to determine which food or ingredient is contaminated and where it came from, a task which can be challenging, particularly considering that multi-ingredient foods are often involved and the same ingredient can be sourced from multiple suppliers around the world.

For this reason, the US Department of Agriculture’s Food Safety and Inspection Service will also collaborate on the project by submitting important bacterial strains from its regulatory testing programme for sequencing at UC Davis.

"It’s possible to look at the genome of each organism and understand where it came from in the world," Weimer noted. "There are ‘forensic footprints’ you can identify to determine which region a particular isolate came from."

Communication problems: challenges of worldwide collaboration

But with so many organisations involved in the project, challenges will be unavoidable. Not only will US governmental bodies, such as the US FDA and the US Department of Agriculture’s Food Safety and Inspection Service play a part in the initiative, Weimer and his team are hoping to build relationships with food companies, state health departments, federal agencies, academia and research institutes worldwide.

"The ambitious project aims to sequence the genomes of 100,000 infectious micro-organisms and make this information available."

"We just had a letter go out through the World Health Organisation (WHO) for the global food network and that has led to an onslaught of queries, particularly from the Middle East and Africa, about the project," Weimer remarked. "We’re also building relationships in Europe, Australia and Asia so people can send in isolates and cultures to be sequenced."

So just how will all of these diverse stakeholders be organised? "Of course, communications becomes a critical piece of how we keep the consortium running," Weimer stressed. "So we’ve created a steering committee, which lays out the ground rules of how people can participate: which organisms get selected to be sequenced first, how and which organisms we want to pull into the project, and so on."

The steering committee is made up of the project’s founding members and all stakeholders that are providing funds for the ambitious scheme, but as more and more organisations jump on board, issues of culture, language and communication are inevitably going to get worse. "We’ll have a monthly steering committee meeting so everyone can be on the same page with where we’re going," Weimer said. "Of course, it will be a challenge to keep everything running, but at the same time, the benefit of having so many stakeholders is worth the communication barriers we have to scale."

The impact that a database of 100,000 food-borne pathogen genomes could have on the detection and mitigation of outbreaks in the US, and indeed all over the world, could be absolutely massive.

Already, according to Weimer, the FDA’s use of next generation sequencing in the US has significantly brought down the length of time it takes to control outbreaks – from months to weeks. And, as various collaborators learn how to pinpoint the source of these deadly pathogens, the prevention, not just the control, of these life-threatening outbreaks will become a more and more realistic possibility.


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