Phages: Ready for the next step?
Bacteriophages play a key role in food safety and animal health.
No one thinks bacteriophages are the magic solution for all bacteria and foodborne diseases. But could they play a key role as another hurdle for pathogens? Absolutely. And they might have to as superbugs grow in numbers.
“Phages will never be as cheap as soap, hot water and bleach,” says Jason Gill, assistant professor of bacteriophage, biology and microbiology, Texas A&M University, based in College Station, Texas. “The traditional food safety methods will always be mainstays. But as phage products develop, with new products developed based on a reliable cold chain, they can be useful for minimally processed and fermented foods, in particular.”
For two decades, scientists have cautioned against excessive antibiotic use. Now, about 18 strains of bacteria have become superbugs that resist most drugs. Roughly 23,000 people die in the U.S. each year from antibiotic-resistant infections.
Bacteriophage cocktail treatments were used in the 1920s and 1930s before penicillin was available. Afterward, they fell out of use for decades until the 2000s when researchers began re-thinking their value in food and pet food safety and medicine.
Phage viruses work by infecting specific bacterial species or unique strains within that species, leaving beneficial bacteria intact.
Phages are registered as processing aids, notes Gill, so many companies that use them don’t advertise their use to maintain a clean-label advantage.
“Most products today are used to fight Listeria, which is the biggest problem for things like minimally processed produce, cold cuts and smoked salmon,” says Gill. “Phages can be applied when the product is packaged because they won’t change the taste or flavor or toward the end of processing.”
Phage products that fight Salmonella also exist, but are still looking for the right niche in the production cycle, he says. “Look at hot dogs and sausages — when do you apply them and where will they be most cost effective?” says Gill. “Upstream, downstream or sprayed on conveyors and rollers?”
In poultry barns, for example, the phage products Gill has seen are not registered for live animals but could be used in chill water and on carcasses. “It might be effective if phages were put in the chill water, but that is changed out multiple times so that could be too expensive,” he says. “Phage manufacturers have approval though to spray carcass parts.”
Ready-to-eat products, beef parts and trim and pre-slaughtered animals also have approval to use phage cocktails to combat Salmonella and Shigella from the USDA Food Safety and Inspection Service (FSIS), notes Gill.
Phage products may be approved to fight bacteria in certain meat and poultry parts, but they haven’t found mainstream acceptance yet from processors. What factors are holding them back?
“Phages have to be stored refrigerated because they are generally less stable at room temperatures,” Gill says. “This quality is good though for fighting Listeria because it can still grow in cold temperatures.”
"The cost of [phage] production is relatively low compared to the burden of foodborne diseases ..., product recalls and damage to company reputation."
— Stanley Maloy, Ph.D. College of Sciences at University of California, Irvine
Phages also work better against pathogens that are metabolically active, such as E. coli on hides, notes Gill.
These factors can lead processors to question their efficacy. How large of a magnitude can they expect, after all? Also, phages aren’t always compatible with other interventions.
“There are chemical sanitizers used in production that can kill phages,” says Stanley Maloy, Ph.D., professor and dean of College of Sciences at University of California, Irvine.
That’s why phages are normally used at the end of processing before packaging, or at the very start of processing as with cattle hides, Gill says.
Cost is also still a factor. Phages are not the cheapest food safety method. They cost more than hot water, sanitizers and lactic acid. Processors, however, may get a return from their economies of scale.
“Phages are not the cheapest intervention, but they offer high versatility in any step during processing and target the right bacteria,” Gill says.
Companies such as Chipotle, for example, have had local supply chain issues, says Gill, that make it harder to validate and control food safety protocols compared to using one large supplier.
“If phages were put in as another part of its food safety hurdle system, maybe they could back up other interventions,” says Gill.
There are also no phage products on the market to target Campylobacter and all of the “Big 6” pathogens (E. coli, Hepatitis A, Nontyphoidal Salmonella, Norovirus, Shigella, Salmonella Typhi) because their bacteria are very diverse. Usually, phage cocktails only use three to four phages to cover bacteria ranges.
In addition, phages are not 100 percent effective — not that other sanitizers are. “Let’s say there are 10,000 bacteria on the surface of a meat carcass,” Maloy says. “A phage application may eliminate them by 100-to 1,000-fold, but there will still be about 10 pathogens left.”
For phages to work, they have to access the bacteria, which can be tricky depending on the structure of the beef, such as areas with flaps, Maloy says.
Preparing for the future
The main way to apply phages is through strains, Maloy says.
“However, chicken is dipped into and processed in vats,” he says. “There’s tremendous evidence of the efficacy of phages. But production issues can be difficult.”
Pre-harvest approaches with phages could potentially be the most effective method because it decreases the aforementioned challenges, Maloy says.
“One chicken, for example, can contaminate the surface with other chickens,” he says. “So poultry processors are more likely to accept phage applications than beef.”
Phages have been accepted and are widely used in pet foods (one-third are contaminated with Salmonella), lunch meats (sprays work best), melon, lettuce and other produce, says Maloy.
“The cost of [phage] production is relatively low compared to the burden of foodborne diseases being transmitted to consumers, product recalls and damage to company reputation,” Maloy says.
In addition, some human infections are being addressed and treated with phages through emergency interventions or clinical trials, Maloy says.
Once phages received attention as a medical treatment, we have seen more acceptance in the food industry to using them, he says.
“People are also looking at using phages in medicine and animal health to decrease antibiotic use,” says Gill. “Regulatory pathways are stricter for medicine, but they are being explored right now. There’s a lot of interest.”
Due to consumer concerns about foodborne diseases, phage applications should continue to increase or even become widespread in five years, Maloy says.
“In five years, we’ll see an increase in production and delivery mechanisms and increased customer acceptance,” Maloy says. “And a strong driver for bacteriophages in the production line will be their role in decreasing challenges due to the costs of foodborne illnesses.” NP