By: Ryan Robinson, PhD

During recalls, such as the latest recall of Nutty Infusions cashew butter for Listeria, many have asked us how health agencies find bacteria in products. With new technology and the refinement of current technology, we are starting to find contamination in foods easier than ever before.

A Little History Lesson

In the late 17th century, a Dutch draper by the name of Antonie van Leeuwenhoek began tinkering in glass lens manufacturing. His original intent, as recorded in the annals of history, was to better assess the quality of thread he was using to manufacturer linen products.  The draper’s interests soon shifted though, and he developed a profound interest and passion for the production and use of high-quality optical lenses to observe the natural world.  As van Leeuwenhoek’s lenses continued to improve, and his methods became more sophisticated, so did the resolution with which he could observe the tiny world around him.

In 1676, van Leeuwenhoek submitted the first observations of self-sustained single-celled organisms to the Royal Society in London. This early work into understanding the microbiological world was initially met with skepticism and contempt (as are most groundbreaking scientific findings), but eventually his findings were accepted and celebrated by the scientific community at large. The early observations, recorded by hand by van Leeuwenhoek as he peered through his hand-crafted microscope, earned him recognition as the father of modern microbiology. They prompted further study into the tiny world around us, and enabled us to study and combat the microorganisms that result in so much suffering around the globe.

Today, a rich tradition of technological advancement persists in medical microbiology.  Microscopes, similar to van Leeuwenhoek’s early prototype in principal but vastly more advanced, still play a critical role in identification and analysis of dangerous pathogenic organisms. Other modern tools and techniques have also joined the fray as weapons in the fight against the microbial causes of human illness and suffering.

One technique, recently employed by the CDC and FDA to help combat Listeria infection, is whole-genome sequencing. Whole genome sequencing of Listeria bacteria, collected from infected patients and contaminated food, helps epidemiologists track infections, identify sources, and move rapidly to stem the tide of infection before more people fall ill. The key to whole genome sequencing of Listeria is looking at very, very small changes (smaller even than can be seen by a powerful modern microscope) in the bacterial genetic makeup.

What is a genome/What is genome sequencing?

To understand whole genome sequencing, one must first understand the gene. Most readers are likely already familiar with the concept of a gene: a string of nucleic acids that carry a set of instructions for producing some form of heritable trait. In human beings, genes are passed from parent to child and carry instructions that define physical traits like eye color or hair color. Bacterial organisms also have genes that are passed on to their offspring. Genes in pathogenic bacteria are responsible for carrying traits that make them particularly virulent and dangerous: things like the ability to an ability to withstand and reproduce in cold-temperatures, or a resistance to certain antibiotic compounds.

The term “genome” is used to describe the entire collection of genetic material (DNA) within a given organisms. Sum up all of your genes, as well as any DNA that doesn’t code for any specific trait, and you’ll have your “genome”. By extension, genome sequencing is the process of identifiy the specific, sequential chemical code that makes up the entire genome.

How does whole genome sequencing help in the fight against Listeria and other dangerous bacterial organisms?

The answer lies in the ability to see and note very small differences in the bacterial DNA. Over time, the genome in any organism shifts and changes. Tiny, random alterations in an organisms DNA (mutations) accumulate as a byproduct of exposure to various environmental factors, or simply as a product of plain chance. These tiny changes are passed on to the organism’s offspring, then on to their offspring’s offspring, and so on ad infinitum. The result is that a hypothetical strain of Listeria found in ice cream produced in Kentucky will be genetically different than a strain of the same bacteria found on produce in New Mexico.

The changes are, of course, so small as to be imperceptible using conventional microbiological methods. Both of our hypothetical strains will look like Listeria to a microbiologist looking through a microscope. Just as not all genetic changes in human beings are visible to the naked eye, not all genetic changes in bacterial pathogens like Listeria are visible through the lens of a microscope. To see these changes, and to understand them we must carefully analyze the genome sequence of each strain, comparing the specific genetic sequence carried by both strains against each-other.

At first glance it might seem pointless to track these tiny imperceptible changes. After all, both strains will make you sick, why concern ourselves with the minutia? This data has more value to researchers and epidemiologists than meets the eye, though. By tracking genetic variants researchers can link illnesses caused by the same contaminated food, even across vast geographic distances (if two strains of bacteria come from the same source, they will have a very similar genetic sequence). By comparing these genetic changes to those found in bacteria on identified, contaminated food-products these researchers can also rapidly track down the probable source of an outbreak, and help to prevent its spread. Using this powerful technology, researchers can even carefully monitor the development and spread of bacterial strains that carry particularly dangerous genes, like those associated with antibiotic resistance.

What promise does whole genome sequencing hold in the future?

The future is rife with promise (but also with bacteria)! As populations continue to grow, and food-safety standards become increasingly lax we are likely to be presented with a variety of new challenges. Recently published CDC data indicates that the incidence of certain kinds of foodborne illness are actually on the rise, despite the prevalence of new technology. Even when outbreaks or illnesses are not the word of the day, we are often beleaguered by news stories of contaminated food products like the recent cashew butter or raw milk incidents.

There is far-reaching hope that advanced technology will help us treat those with foodborne-illness, or ideally prevent contaminated foods altogether. Presently, whole genome sequencing is used exclusively to track, identify, and hopefully prevent the spread of outbreaks of dangerous pathogenic bacteria like Listeria. It is a valuable endeavor in its own right (an ounce of prevention is worth a pound of cure), but hopefully it is still shy of its greater future potential.

 

 

Additional Reading:

CDC Publication: Whole genome sequencing and Listeria

Köser, C. U., Ellington, M. J., & Peacock, S. J. (2014). Whole-genome sequencing to control antimicrobial resistance. Trends in Genetics, 30(9), 401-407. doi:10.1016/j.tig.2014.07.003

Gilmour, M. W., Graham, M., Domselaar, G. V., Tyler, S., Kent, H., Trout-Yakel, K. M., . . . Nadon, C. (2010). High-throughput genome sequencing of two Listeria monocytogenes clinical isolates during a large foodborne outbreak. BMC Genomics, 11(1), 120. doi:10.1186/1471-2164-11-120