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Food Pathogen Interventions: Phasing in Phages

Editor’s Note: This article is the continuation of a series on emerging techniques introduced at the Foodborne Pathogen Interventions Symposium in Seattle on April 27. The event was hosted by the Seafood Product Association. Today’s installment focuses on bacteriophages, presented by Dr. Alexander Sulakvelidze of Intralytix™.

The word “virus” usually sends people grabbing for the hand sanitizer. But some of these microorganisms actually serve as sanitizers themselves, and can contribute to the safety of the food supply. 

bacgteriophageXX-featured.jpgBacteriophages, or “phages”, are naturally occurring viruses that exist only to target and kill bacteria. They are the oldest, most ubiquitous organism on the planet, with anywhere from 1030 to 1032 of them existing at once in the air, soil, water, food and animals, according to Dr. Alexander Sulakvelidze, Associate Professor of Molecular Genetics and Microbiology at the Emerging Pathogens Institute. 

Although humans have been isolating phages from the environment to help fight disease since the turn of the 20th century, these agents are just beginning to be used on foods, according to Sulakvelidze, who helped patent ListShield™, the first bacteriophage approved for contact with food. 

Products such as this are made up of what Sulakvelidze calls a “cocktail” of different bacteriophages, all of which target a specific type of pathogen. For example, ListShield™ attacks only Listeria monocytogenes.

Phage treatments are mixed with water and applied as a spray. Once on food, phages inject their DNA material into their targeted bacterial cells, where they replicate until they burst the cell open.

And they’re good at what they do. Bacteriophage solutions routinely kill anywhere from 95 to 100 percent of their targeted bacteria in lab tests.

Bacteriophages offer an advantage over other pathogen-killers in that they are selective, and will not harm any other, beneficial organisms in food, thus preserving its original state.
“You will not be able to tell the difference in terms of taste, appearance, nothing,” Sulakvelidze said. “It’s almost like it’s been sprayed with a little bit of clean water.”

This makes bacteriophages ideal for use on organic and ready-to-eat foods.

But their selective nature also means that phages cannot be used as a universal preventative for all types of foodborne illness.  Each phage will only kill one type of pathogen.

Another concern related to phages is that pathogens might eventually build up resistance to them. In an era when antibiotic-resistance is becoming an increasing threat, phage-proof superbugs would be less than desirable.

No need to worry, said Sulakvelidze. While bacteria are indeed capable of mutating to become immune to these viruses, phage cocktails contain more than one phage targeted at each strain of bacteria, so that even if a microbe develops immunity to one phage, it would most likely be killed by others.

And while bacteria become resistant to antibiotics quickly because of the wide use of these drugs on farms, phages are used in a much more controlled environment. A phage isn’t intended to be sprayed in the chicken house because “it’s a very complex environment and it will trigger resistance very quickly. What we are doing is spraying phage on the finished product before it’s packaged. So basically the exposure you have is within that package,” he said.

In the event that a phage does stop working on its target bacteria, Sulakvelidze said, his company has FDA approval to isolate new bacteriophages and substitute them for ones that have ceased to be effective.

As an added comfort, even if phages were to be used on 100 percent of foods in all U.S. processing facilities, and consumed at the highest rate (what a 24-year-old male eats), they would increase the amount of phages in the environment be a mere .0000000000000000006 percent, Sulakvelidze reported. That’s 18 zeroes.

So why, with its low environmental impact and high success rate, hasn’t phage been more widely-adopted yet?

“When we started, there was a big yuck factor,” said Sulakvelidze. “You’re going to be putting viruses on food. And that factor is still out there, but that’s simply because people don’t realize they’ve already eaten them.”

In fact, he said, everyone in the U.S. sheds an average of 3×10^10 E. coli phages every day.
“What we’re talking about is taking a little bit of phage from the same or very similar food and putting it back into the food that might not have had enough [phages] to make it safe.”

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