Bacteriophages (phages) have been used as tools to address several of the emerging global issues that now plague humanity. Food safety is one of the areas where the unique characteristics of phages have shown promise as effective biocontrol agents of bacteria. Phages are the natural viral predators of bacteria and have evolved over billions of years to efficiently bind, infect, and kill their host bacteria with a high degree of specificity and speed. What’s more, phages are ubiquitous and naturally exist on food surfaces, are regularly consumed by humans, and do not influence the organoleptic profile of the products they come in contact with (Moye, Woolston, and Sulakvelidze 2018, O’Sullivan et al. 2019). Since the topic was last addressed in Food Technology in 2014, interest in general phage research as well as applications of new food-related phage technologies has grown significantly as emerging methodologies and technological advances in genetic engineering accumulated and became less expensive to employ (Wheatley et al. 2020, Peng and Chen 2020).

This ever-expanding niche in the field of biotechnology boasts a number of new and exciting developments that have caught the eye of many food processors along the farm-to-fork chain. Examples of phage-based technologies currently on the market include Agriphage (Certis USA), which is being used to control bacterial spot and speck on tomatoes and peppers; EcoShield (Intralytix) and PhageGuard E. (PhageGuard), which target E. coli O15:H7; PhageGuard S. (PhageGuard) and SalmoFresh (Intralytix), which target Salmonella spp.; and ListShield and ShigaShield (both from Intralytix), which target Listeria monocytogenes and Shigella spp., respectively (Moye, Woolston, and Sulakvelidze 2018). The continual global impact of food outbreaks means that new and innovative ways for combating these dangerous bacterial food and water pathogens are actively needed. Researchers can take advantage of natural systems (i.e., phage infections) that have been so evolutionarily successful in controlling their targeted bacteria’s population, they’ve gone viral. After all, the enemies of our bacterial enemies are promising food safety friends.

In the early 1900s, phages were administered to patients infected with bacterial pathogens as a means to control the infection. This practice is called “phage therapy”: where a cocktail of phages that target the same bacterial host(s), often via different surface receptors, are administered together in order to cover a wider number of bacterial strains within this cumulative host range. Although using phages was originally met with enthusiasm, the discovery of penicillin in 1928 combined with controversies within the scientific community over the efficacy of phage treatments (due to inconsistent results and poorly controlled experiments) resulted in phage research being effectively abandoned in the United States at the end of World War II. In many Eastern European countries and the former Soviet Union, however, phage research has continued to thrive and is widely practiced (Pires et al. 2016). Phage cocktails have been successfully used in the past for bacterial-induced diseases like cholera and dysentery (Kutter 2009), and more recently in a highly publicized case of multidrug resistant Acinetobacter baumannii in San Diego (Schooley et al. 2017).

In the United States, phage therapy has only been approved for “compassionate use” by the U.S. Food and Drug Administration (FDA) although many other phage-based technologies have been approved by U.S. regulatory agencies, including the FDA, the U.S. Department of Agriculture, and the Environmental Protection Agency (O’Sullivan et al. 2016). Some of the most popular phage products, such as ListShield, have been reliably used in the United States since the mid-2000s, with many products having also achieved GRAS (Generally Recognized as Safe) status for equally as long (Endersen et al. 2014). Similar phage applications are prevalent in European countries, improving upon both food and water safety as well as highlighting the immense versatility of these predators of bacteria. As an example, a prominent biotech company based in the Netherlands, Micreos, has been producing phage-based biocontrol technologies (where “phage biocontrol” is defined as using high concentrations of phages to specifically target and eradicate relevant foodborne or waterborne bacterial organisms) for food safety applications since 2010 (Kazi and Annapure 2016).

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