The increasing global attention to the threat of antibiotic resistance has spurred research and development of antimicrobial alternatives. Once such alternative is bacteriophages. Bacteriophages are viruses that infect and kill bacteria. There are thousands of different types and they are so abundant in the environment – an estimated 1030 live on the planet – that “we eat thousands of phages a day,” says Manan Sharma, a research microbiologist with USDA’s Agricultural Research Service. After they were discovered in 1915, scientists tried to use them to treat diseases like cholera. But the discovery of powerful antibiotics caused phage therapy to be essentially abandoned. That interest has returned in the 21st century as antibiotic resistance increases. But it’s important to remember that bacteriophages are not infallible either. Similar to bacteria developing antibiotic resistance, “the target [of a phage] can change and most likely will change because it’s a contestant evolutionary battle,” Sharma says. Each bacteriophage is antagonistic toward specific bacteria or serotypes. Biotech companies have been working to isolate individual phages and define their hosts. “You have phages that are specific for E. coli or Listeria or Salmonella,” Sharma says. “For example, you’ll have a phage that’s specific for E. coli O157:H7 that may not be specific for E. coli O26.” So companies that commercially produce bacteriophages try to find phages that attack a broad set of hosts or create cocktails of phages with narrow targets. Sharma’s lab has studied the effectiveness of some of these commercially-produced bacteriophages on cucumbers and lettuce inculcated with E. coli or Salmonella and found as much as a 2-log reduction. A 5-log reduction, or a 100,000-fold reduction, in bacterial counts is the goal for food safety interventions, but Sharma says even though bacteriophages may not be able to eliminate the target pathogen population, hopefully you’re able to reduce it before subsequent treatments or so that storage conditions will not allow the bacteria to grow. Isolating the right bacteriophages takes a lot of work, but so does figuring out the best application of them. Is the best chance of reducing the bacterial population in the field, during packaging, in the wash water, or during another step in the production chain? “We found in our work that a direct spray application has given us the best results,” Sharma says. “Incorporating them into wash water with lettuce hasn’t really yielded the results that we would have liked to have seen.” Each commodity’s individual risks and production cycle could call for a different application. The consensus among microbiologists is that bacteriophages don’t harm humans, but Sharma wonders how the general public would react to them if they become a widely used food safety intervention. Phages are essentially “natural” since they come straight from the environment, but plenty of people could view them as “injecting viruses into food.” “I don’t know if consumers would want that,” Sharma says. “I’m not scared of consuming bacteriophages because I probably just did with the turkey sandwich I had for lunch.” Bacteriophages are not the ultimate solution to solving the antibiotic resistance crisis, but they could be an important piece of the puzzle. After decades at the wayside, phages are “something old that has become new again,” Sharma says, and they could probably benefit from more research and development.