Is there a future for phages in business? The medical industry and universities seem to think so. And now the agriculture industry seems to be embracing these targeted pathogen killers, as well.

“Last year, there was still some hesitancy on accepting phages,” says Stanley Maloy, Ph.D., associate vice president for research and innovation and professor of biology at San Diego State University. “But they are becoming more prevalent because their efficiency is opening doors for more applications.”

Medical advances with phages have certainly paved the way for phages to target pathogens in agriculture. It was just three years ago that Dr. Tom Patterson’s treatment at UC San Diego School of Medicine with intravenous bacteriophage therapy received widespread attention for saving his life from a drug-resistant infection. This year, the U.S. Food and Drug Administration (FDA) has approved the first clinical trial in the United States for an IV-administered bacteriophage-based therapy to kill drug-resistant bacteria at UC San Diego.

For the last few years, the Howard Hughes Medical Institute also has worked with more than 100 colleges and universities to help students achieve real-world experience with research projects, such as working with the Phage Hunters Advancing Genomic and Evolutionary Science (SEA-PHAGES) project. Aspiring scientists will graduate with practical experience with phages.

Phages may in fact be the industry’s best kept secret. But not for much longer. The meat and poultry industry are on the cusp of more phage treatments and uses in the next year or two, Maloy says.

“A lot of exciting developments with phages have occurred this year, partly driven by the success of human trials because they’ve raised positive attention,” says Maloy.

New or recent phage cocktails target Salmonella on commercial broiler farms and the shigella pathogen. “Currently, phage cocktails are being used in post-harvest interventions to target Listeria in fish and ready-to-eat meats,” Maloy says. “Escherichia coli O157:H7-targeted phages are used in cattle washes and for processed chicken and pork.”

Registered products targeting Salmonella are currently approved, according to the USDA Food Safety and Inspection Service (FSIS) website. For Salmonella phages, the challenge is picking the best application for poultry, eggs and pork. 

“In the poultry market, where do you apply the phages — the farm or plant?” says Jason Gill, Ph.D., assistant professor, bacteriophage biology and microbiology, Texas A&M University, based in College Station, Texas. “Cost issues still exist.”

For beef products, a current phage product targets pre-harvest interventions, says Gill. “More phage products for STEC (Shiga toxin-producing E. coli) could be developed for beef, as well,” he says. “There are other Shiga toxins than E. coli O157:H7.” 

Phages are appealing because they can be used in a variety of ways to target a particular kind of bacteria. “A lot of bacteria are good, and we don’t want to kill them, only harmful bacteria,” says Maloy.

Disinfecting surfaces

For now, phages are commonly used as surface disinfectants or food additives for farm animals, which has FDA approval. “As a disinfectant or food additive, there is strong evidence it works; so the industry has substantially increased using it,” Maloy says.

Disinfectants are applied as sprays in concentrated liquids as a wash or rinse to cleaning surfaces or the product, such as ready-to-eat (RTE) meats before packaging. 

“Phages can stay active at refrigerator temperatures, and you don’t have to worry about removing them from the product after they are sprayed,” Gill says. “They have no effect on product quality, unlike produce applications.”

As a food additive, phages are integrated into the animals’ food. “Phages are usually applied in this manner because injecting phages into the bloodstream is not effective on a broad scale,” says Maloy.

Veterinarians are interested in phages as an alternative to antibiotics to prevent drug resistance. “A fair amount of use is still experimental when treating living animals,” Maloy says. “Most people accept the idea that when possible live animals do much better with vaccines — they are protected for a long period of time.”

Keeping costs down

Costs, however, always remain an issue. “As a rule of thumb, costs are always bigger in agribusiness than the medical field,” Maloy says. “But availability is increasing along with those skilled in using them. So, costs are decreasing and should continue to decrease.”

The cost of producing phage cocktails is still a challenge, and more work needs to be done to identify effective phage cocktails; however, collections are building of cocktails that are effective against human and animal pathogens, Maloy says.

Another hurdle is delivering the cocktail effectively to cattle’s gut or rumen, which is a problem for chickens too, says Maloy.

Moreover, conventional applications such as heat or bleach can disinfect surfaces much cheaper than phages.

But phages do provide another hurdle against pathogens, so they can be considered a part of [HACCP] barrier plans for combating pathogens, says Gill.

“Phage manufacturers are working with certain processors to see where their phages can be most cost effective,” Gill says. “It’s an expanding market, so we need to find the right application for them.”

Focusing on the future

As clean and transparent labels increase in popularity, it stands to reason phages could be more popular as they are not listed on labels, are all-natural and safe to use, Gill says.

“Phages aren’t seen as being ‘scary’ anymore,” Gill says. “Twenty years ago, people in the industry may have been worried about them, while those in the medical industry were receptive to them as bacteria killers.”

Now, the industry may be more put off by their clinical and economic applications — such as how scalable they are.

“They are not scientific concerns but economic concerns,” says Gill. “For food safety, phages have market acceptance. So how much do you grow the product? Will it stay a niche product or become as mainstream as lactic acid?”

The answer again depends on phages’ cost. If they are broadly used, they will be cheaper to make and achieve economies of scale.

“I expect more companies to use phages for particular applications in agriculture,” Maloy says. “In a couple years, they should be reasonably commonplace.” NP