Whether they are killing livestock and crops or contaminating ready-to-eat foods, bacteria cause major problems in the food industry. To solve these problems, scientists are thinking small. Many studies have shown that bacteriophages (i.e., phages or viruses that infect bacteria) can eliminate problem bacteria throughout the food system, from controlling plant pathogens to eliminating bacteria in produce, meat, and other food products. While several commercial phage products are on the market, continued exploration of the bactericidal potential of phages in food production and optimization of their use will be essential to expand applications.
What are phages and how are they used in the food industry?
Wherever there are bacteria, there are phages - which means that phages are practically everywhere. actually thereare estimated 100 nonillion (1031) phages not planet. This gigantic population is incredibly diverse, as each individual phage has a defined range of bacterial species and strains that it can infect. However, all phages have one thing in common: they attack bacteria, and only bacteria. Humans, plants, animals and other microbes are not targeted.
As such, phages can be used to mitigate bacterial pathogens in all sectors of society. For example,phage therapyinvolves the isolation and implantation of phages that specifically kill the bacteria causing an infection. In the food industry, phages have been explored and applied for the management of bacteria from the beginning to the end of the food processing process.
On the farm and in the field: pre-harvest applications of phages
The loss of animals and plants to bacterial diseases in the pre-harvest phase hassignificant economic costs(billions of dollars) and threatens the stability of the food system. In livestock, antibiotics have been the method of choice for mitigating infections and promoting animal health, although this practice has exacerbated the spread ofantimicrobial resistance. Phages may offer a solution. In fact, researchers found that 3 phages isolated from sewage from a dairy farmwere as effective as antibiotics in relieving mastitis symptoms(an udder infection leading to an estimated$2 billion annual lossin the USA) caused by resistant drugsEscherichia coliin cows. Similar positive results have been demonstrated in controlling a variety of pathogens - including those that can make people sick, such assalmonella,E. coliO157:H7 eCampylobacter jejuni, among others - and in several animals (for example, birds, fish and others).
Phages can also be used tominimize crop loss to bacterial diseases. Application of selected phages to crop seeds or leaves can reduce the pathogen load and decrease the severity and incidence of disease during the growth stage. Already existcommercial phage productsregistered with the US Environmental Protection Agency (EPA) designed to kill pathogens that infect foods such as tomatoes, citrus fruits, apples, pears and more.
Phages to fight foodborne pathogens
In addition to preventing and treating animal and plant diseases, phages are useful for detecting and preventing the growth of foodborne pathogens during and after food processing. For example, scientistsmanipulated reporter phageswhich allowed bioluminescence-based detection of the foodborne pathogen,Listeria monocytogenes,in contaminated milk, cold cuts and lettuce. Foods can also be dipped or sprayed with phage solutions designed to kill pathogens that commonly contaminate them. This application ofphage biocontrol(i.e., the use of phages as antimicrobial agents to reduce concentrations of pathogens in a treated environment) in the food industry has seen the greatest commercial success to date, withvarious products on the marketdesigned to fightSalmonella, E. coli, L. monocytogenesand other bacteria. phagescan also be applied to sterilize surfaces in food processing facilities, such as conveyor belts and food transport racks, which can serve as conduits for bacterial contamination.
What are the benefits of Phage Biocontrol?
Many features of phages make them useful for biocontrol purposes.Thomas Denes, Ph.D., an assistant professor of food molecular microbiology at the University of Tennessee who studies phage-based applications for food safety, highlighted the defined host range of phages as an important benefit. He noted that phages can target pathogens while leaving other bacteria associated with a food (for example, beneficial bacteria in foods like yogurt, kimchi, and cheese) untouched.
Furthermore, phages are not limited by the concentration of their application – they replicate. “In the food processing environment, there are often complex niches or structures that make the delivery of an antimicrobial challenging,” said Denes. "So having an antimicrobial that replicates when it comes into contact with its host means that treatment will be amplified where it's needed, whereas conventional disinfectants or sanitizing agents may have trouble reaching the areas where pathogens are actually surviving or replicating." like the nooks and crannies of food processing equipment (or the food itself).
Amit Vikram, Ph.D., senior researcher atIntralytix, Inc., a biotechnology company that produces phage-based products to eliminate foodborne pathogens, pointed to the safety of phages as another advantage. Compared to hazardous chemicals that can harm workers and must be disposed of properly, phages do not pose a risk to people working or consuming food. Furthermore, “[phages] have great efficacy without affecting food, texture, properties and flavors,” explained Vikram, which makes them attractive even to food producers concerned with removing microbial contaminants while maintaining the integrity and essence of a food. .
What are the challenges associated with Phage Biocontrol?
Still, phages are not perfect. On the one hand, the defined host range that makes phages great can also be a downfall. "In food safety contexts, a food producer would purchase a phage product to manage the risk of a target pathogen," said Denes. However, the phages in this product may not be effective against all strains of a bacteria that may be present, of which there may be many. Vikram noted that using mixtures of phages with different host ranges could be a way to address this limitation, although these mixtures still do not cover all strains of a pathogen that could pose a threat.
Phages also do not move in search of their hosts. Because of this, it is critical to properly coat foods with phages to ensure they reach their target pathogens. This is easier said than done. “Different foods have different types of surfaces,” explained Vikram. “Raw poultry products have a rougher surface than a sausage, which has a smoother surface. Green leaves have a very large, very rough and very wavy surface”, which makes the application of phage biocontrol “extremely challenging” and something that requires further optimization.
Bacterial resistanceto phages can also pose a problem. Denes said the risk of resistance may depend on how the phages are being used: are they applied to ready-to-eat foods at the end of production, or are foods treated at the beginning of processing? In the latter case, there may be more opportunity for the phages to select for resistance. With that in mind, Denes' lab found that in vitro coevolution experiments with phages andL. monocytogenes allowed the isolation of laboratory-grown phages that could infect resistant strains of the pathogen. The results suggest that such experiments can help to improve host range and the effectiveness of phage biocontrol. Usingmixtures of phages with different infection strategiesare also useful in this context, as they can reduce the frequency with which phage-resistant bacterial mutants arise. If a resistant mutant appears, Vikram pointed out that it is possible to isolate phages with activity against this mutant from natural sources.
What are the next steps?
Until now, phages are mainly being used for postharvest applications, particularly to controlsalmonellagrowth in poultry, although its potential in other facets of the food system (eg crops, livestock, production) is becoming more appreciated. Vikram emphasized that education will be key to expanding the use of phage products in the food industry. “There are still a lot of companies that don't really understand phage technology per se,” he said, describing how many companies confuse phage products with chemicals or are concerned about putting viruses on food (remember, these are viruses that only infect bacteria). Vikram also thinks that educating regulatory agencies, including the US Food and Drug Administration (FDA), about how phages work could help facilitate more streamlined approval of phage-based products.
For Denes, the future depends on research. “I think we are now at a stage in the field of applied phage research where we are identifying ways to overcome some of the challenges [associated with phage biocontrol], such as emergence of phage resistance, diversity of environmental conditions that we need to function, and the diversity of pathogens that we need to be able to target,” he said. "I think we're getting there by understanding the mechanisms of [phage-host] interactions and identifying tools such as phage evolution [or] engineering."
That said, phages are not the be-all and end-all for controlling bacterial pathogens in the food system. They are just another tool that, when combined with proper food handling, storage and other control methods, help fight pathogens and ensure food safety – from farm to plate.
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FAQs
What foods have phages? ›
Foods such as honey, licorice, oregano, and hot sauce have an antimicrobial effect and some of them trigger phage production in our gut.
What are phages in food processing? ›In biosanitization, phages or the enzymes that they produce are mainly used to prevent the formation of biofilms on the surface of equipment used in the production facilities. In the case of biopreservation, phages are used to extend the shelf life of products by combating pathogenic bacteria that spoil the food.
Which food pathogens can be targeted by the use of bacteriophage? ›[10] who demonstrated the use of phage cocktails to control Campylobacter in broiler chickens, following the birds from farm to the processing plant. Phage cocktails were selected to target C. jejuni and C. coli.
What is the method involving phages? ›Phage therapy is a way of delivering virulent phages to a clinically ill patient to rapidly kill pathogenic bacteria. It involves the use of lytic phages, bioengineered phages, and purified lytic proteins of phages to infect and lyse bacteria at the site of infection.
Are phages toxic to humans? ›Since phages consist mostly of nucleic acids and proteins, they are inherently nontoxic. However, phages can interact with immune systems, at least potentially resulting in harmful immune responses, though there is little evidence that this actually is a concern during phage treatment.
Where are phages most likely to be found? ›Also known as phages (coming from the root word 'phagein' meaning “to eat”), these viruses can be found everywhere bacteria exist including, in the soil, deep within the earth's crust, inside plants and animals, and even in the oceans. The oceans hold some of the densest natural sources of phages in the world.
What are the 3 types of phages? ›There are three basic structural forms of phage: an icosahedral (20-sided) head with a tail, an icosahedral head without a tail, and a filamentous form.
What are phages for food safety? ›As the natural enemy of bacteria, phages specifically kill pathogens like Salmonella and Listeria, and leave the good ones intact. They are green, smart and easy to apply on food via spraying, misting or dipping.
Are phages good or bad? ›HIV, Hepatitis C, and Ebola have given viruses a bad name, but microscopic phages are the good guys of the virology world. Each phage specializes in overtaking certain strains of bacteria—for example, staph, strep, and E. coli—which they attack and use as a host to multiply.
Do bacteriophages target humans? ›Called bacteriophages, or phages, these viruses cannot infect human cells. Phages are incredibly diverse and exist everywhere in the environment, including in our bodies; in fact, humans contain more phages than human cells. Phages are naturally occurring viruses that attack and kill bacteria.
Which are the most commonly used bacteriophages? ›
M13 and lambda phage are commonly used bacteriophages.
How are bacteriophages used in agriculture? ›Phage biocontrol has been used in various agricultural settings since 1935 to treat plant diseases caused by bacteria. Erwinia amylovora is one of the most widely studied plant pathogens.
Can phages replace antibiotics? ›They are the most common biological entities in nature, and have been shown to effectively fight and destroy multi-drug resistant bacteria. Namely, when all antibiotics fail, phages still succeed in killing the bacteria and may save a life from an infection.
How do you collect phages? ›Phages are purified by removing, picking off, a well isolated plaque using either a Pasteur pipette or more crudely, but just as effectively, a wire loop. Using a sterile Pasteur pipette the area around the plaque is stabbed and pieces of soft area are 'sucked' into the pipette.
Why are phages not used? ›Phages may trigger the immune system to overreact or cause an imbalance. Some types of phages don't work as well as other kinds to treat bacterial infections. There may not be enough kinds of phages to treat all bacterial infections. Some phages may cause bacteria to become resistant.
Are phages allowed in the US? ›Yet, phage therapy has largely existed on the fringes of medicine, particularly in Western countries like the U.S., where it is occasionally approved for compassionate use (i.e., used on an emergency basis when no other approved therapies are available).
Why don't we use phages instead of antibiotics? ›Second, phage takes a longer time to employ in a treatment compared to antibiotics. Because a single type of phage can only infect a few species of bacteria, phage selection has to be done with care.
What is a natural enemy of bacteria? ›Bacteriophages are, therefore, the natural enemies of bacteria. In nature, both bacteria and bacteriophages are necessary to keep microscopic ecosystems working properly.
How many bacteria are killed by phages every day? ›Bacteriophages in nature
According to Forest Rowher, PhD, a microbial ecologist at San Diego State University, and colleagues in their book Life in Our Phage World, phages cause a trillion trillion successful infections per second and destroy up to 40 percent of all bacterial cells in the ocean every day.
Generally phages are pretty stable if the environment is not hostile. They are broken down in UV light, and can be damaged by abrasion, or exposure to chemicals, but researchers have been known to keep phages in their fridges for over 40 years with no reduction in titre (Ackerman HW, personal communication).
What diseases are caused by bacteriophage? ›
These include diphtheria, botulism, Staphylococcus aureus infections (i.e. skin and pulmonary infections, food poisoning, and toxic shock syndrome), Streptococcus infections, Pasteurella infections, and cholera, Shiga toxin-producing Shigella and Escherichia coli infections, and Pseudomonas aeruginosa infections.
What bacteria eats viruses? ›Tiny, pond-dwelling Halteria ciliates are virovores, able to survive on a virus-only diet, researchers report December 27 in Proceedings of the National Academy of Sciences. The single-celled creatures are the first known to thrive when viruses alone are on the menu.
Does every bacteria have a phage? ›Phages and their biology
Phages have been isolated from every environment in which bacteria exist, and it is believed that at least one type of phage – and most likely many more than one – infects every strain of bacteria.
One could expect as estimated that 1015 phages reside in the human gut, which accounts for approximately 108–1010 phages per gram of human stool depending on the extraction method used [9,10,11,12] and ~109 bacterial cells per gram of stool [13].
What phage kills E coli? ›Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis | Microbiology Society.
What disinfectant to use for phage? ›Three disinfectants which are used commonly in microbiology laboratories were evaluated: Virkon (1%), ethanol (75%) and sodium hypochlorite (2500 ppm available chlorine). The most effective of these was Virkon, which inactivated all six phages rapidly.
Can bacteria become immune to phages? ›Bacteria can develop resistance to phages, as they do to antibiotics.
Has the FDA approved phage therapy? ›The first clinical trial for intravenous (IV) phage therapy gained FDA approval in 2019.
What kills bacteria in the human body? ›Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi.
Can phages enter human cells? ›The Epithelial Barrier. Bacteriophages can penetrate layers of epithelial cells and possibly spread to different areas of the body, including blood, lymph, internal organs, and even the brain.
What are the side effects of bacteriophage? ›
Multiple side effects, including intestinal disorders, allergies, and secondary infections (e.g., yeast infections) have been reported (76). A few minor side effects reported (17, 58) for therapeutic phages may have been due to the liberation of endotoxins from bacteria lysed in vivo by the phages.
Can bacteriophages cross the blood brain barrier? ›Crossing the blood-brain barrier (BBB) is another challenge for most drug vectors and therapy medications. Filamentous bacteriophage can enter the brain across the BBB.
Where is bacteriophage found in the body? ›Bacteriophages, or phages for short, exert significant selective pressure on their bacterial hosts, undoubtedly influencing the human microbiome and its impact on our health and well-being. Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract.
Why are bacteriophages the deadliest? ›From all these, we can conclude that the most abundant killer on the earth- bacteriophage could be given the tag of deadliest being as it devours mercilessly numerous bacteria every second. But they are equally important for conservation and sustenance of life.
Is phage therapy available in North America? ›If you live in (or can travel to) the USA:
All phage therapy in the USA is experimental, so to be eligible for phage therapy, you must have a bacterial infection, and all antibiotics normally prescribed for that infection must have been tried, and must have failed to clear the infection.
Phages won't harm any of your cells except for the bacterial cells that they're meant to kill. Phage therapy has fewer side effects than antibiotics. On the other hand, most antibiotics have a much wider host range. Some antibiotics can kill a wide range of bacterial species at the same time.
Can a bacteriophage be used for treatment of human disease? ›Studies in Humans. Bacteriophages have been used to treat bacterial infections involving different body sites with various preparations.
What is the role of bacteriophage in soil? ›Soil bacteriophages are a vital part of bacterial ecology, as they shape soil microbial communities through facilitating horizontal gene transfer, and constitute a major reservoir of genetic material that contributes to biological evolution and diversity [1,2,3,4].
Why is bacteriophages important in humans? ›Although bacteriophages cannot infect and replicate in human cells, they are an important part of the human microbiome and a critical mediator of genetic exchange between pathogenic and non-pathogenic bacteria [5][6].
What does Russia use instead of antibiotics? ›Phage therapy is used in Russia, Georgia and Poland, and was used prophylactically for a time in the Soviet army. In Russia, extensive research and development soon began in this field. In the United States during the 1940s, commercialization of phage therapy was undertaken by Eli Lilly and Company.
Can phages be used as vaccines? ›
Nowadays, two main types of phage-based vaccines have been widely recognized: (1) phage display vaccines and (2) bacteriophage DNA vaccines [6,10]. The combination of these two strategies has resulted in the development of a third strategy, (3) the hybrid phage vaccine.
What is the strongest antibiotic made? ›Vancomycin 3.0 is one of the most potent antibiotics ever created. It is used to treat conditions like methicillin-resistant Staphylococcus aureus-induced meningitis, endocarditis, joint infections, and bloodstream and skin infections.
How much does phages cost? ›The following is an estimate; costs may differ in your case, depending on the complexity of your condition: out-patient care: $4,000.00 - $6,000.00 US for one nosology, for example sinusitis.
How do you store phages for a long time? ›Phages should be stored cool immediately upon receipt. Don't freeze phage suspensions without adding a cryoprotectant. When stored cool, most of the phages will remain active without significant activity loss for some months.
Can phages carry DNA? ›Bacteriophage have either DNA or RNA as their genetic material, in either circular or linear configuration, as a single- or a double-stranded molecule.
Are phages harmful to humans? ›Since phages consist mostly of nucleic acids and proteins, they are inherently nontoxic. However, phages can interact with immune systems, at least potentially resulting in harmful immune responses, though there is little evidence that this actually is a concern during phage treatment.
Are phages the deadliest thing in the world? ›The bacteriophage, or phage for short, is a virus that specializes in killing certain types of bacteria. They are the deadliest entities on our planet, responsible for the majority of deaths on Earth.
Does the immune system fight phages? ›Cellular Immunity to Phages
Phages also elicit cellular adaptive immunity. When phages are endocytosed and processed by APCs, phage-derived peptides are presented on MHC surface molecules, resulting in B and T cell responses against the relevant viral antigen in vitro (127, 128) and in vivo (93, 129).
Phages occur naturally in the production of fermented foods including sauerkraut and dairy products such as cheese and yoghurt.
What are three examples of phages include? ›Phages are classified in a number of virus families; some examples include Inoviridae, Microviridae, Rudiviridae, and Tectiviridae. Like all viruses, phages are simple organisms that consist of a core of genetic material (nucleic acid) surrounded by a protein capsid.
Do phages live in humans? ›
Bacteriophages (phages) are bacterial viruses that are the most abundant, omnipresent, and diversified biological group inhabiting Earth [1,2]. They are detected in soil, water and in the human body (feces, saliva, sputum, blood, and urine) [3].
How do you prevent phages? ›Generally, prevention strategies (like good laboratory/factory hygiene, sterilisation, decontamination and disinfection) are necessary to avoid bacteriophage contamination.
What human disease is caused by bacteriophage? ›These include diphtheria, botulism, Staphylococcus aureus infections (i.e. skin and pulmonary infections, food poisoning, and toxic shock syndrome), Streptococcus infections, Pasteurella infections, and cholera, Shiga toxin-producing Shigella and Escherichia coli infections, and Pseudomonas aeruginosa infections.
Where are bacteriophages found in humans? ›Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. As such our bodies are frequently and continuously exposed to diverse collections of phages.
Why are bacteriophages safe for humans? ›Bacteriophages (BPs) are viruses that can infect and kill bacteria without any negative effect on human or animal cells. For this reason, it is supposed that they can be used, alone or in combination with antibiotics, to treat bacterial infections.
How many bacteria are killed by phages? ›According to Forest Rowher, PhD, a microbial ecologist at San Diego State University, and colleagues in their book Life in Our Phage World, phages cause a trillion trillion successful infections per second and destroy up to 40 percent of all bacterial cells in the ocean every day.
Do all bacteria have phages? ›Phages and their biology
Phages have been isolated from every environment in which bacteria exist, and it is believed that at least one type of phage – and most likely many more than one – infects every strain of bacteria.
Phages aren't like other viruses that make you sick. They can only infect bacteria.
Why don't we use phages? ›Phages may trigger the immune system to overreact or cause an imbalance. Some types of phages don't work as well as other kinds to treat bacterial infections. There may not be enough kinds of phages to treat all bacterial infections. Some phages may cause bacteria to become resistant.
How do you get rid of phages? ›1) If you can throw out the contaminated culture, do it; but don't just put some vircon into it, autoclave the culture to kill the phage. 2) Discard all of the solutions you used to prepare the culture. 3) Clean the shaker, your bench and other surfaces which might have contacted the contaminated culture, with ethanol.