Introduction
Food safety is a crucial global concern, with 600 million cases of people suffering from foodborne illnesses each year and 420,000 dying from them 13 . Traditional treatments, such as pasteurisation and chemical preservatives have proven useful, although they have limitations. Whilst pasteurisation is successful at killing many diseases, it can occasionally change the flavour, texture, and nutritional value of food 18 . Chemical preservatives, on the other hand, can cause the development of resistant bacterial strains and pose possible health hazards when consumed over time. These resistant bacterial strains are detrimental to immunological health because they can render normal therapies ineffective, resulting in more severe and persistent infections that are difficult to cure 30 . For example, several bacterial strains recovered from seafood revealed that a large percentage of the isolates tested (75.86%) were resistant to at least one antibiotic or biocide, which is a type of chemical preservative used in food, with 6.90% resistant to at least three biocides and three antibiotics 11 . Bacteriophages, viruses that specifically target and kill bacteria, are one novel option that is becoming increasingly popular. This article investigates how bacteriophages can improve food safety, including their mechanisms, applications, and potential problems.
What are Bacteriophages?
Bacteriophages are viruses that infect bacteria. Discovered in the beginning of the 20th century, they are extremely specific to their bacterial hosts, making them suitable for targeting harmful bacteria while preserving beneficial microflora. These viruses strictly stick to the bacterial cells and introduce their own genetic material into them. The phage then hijacks the bacterial machinery and allows for viral replication, eventually leading to cell lysis and death 2 . As self-propagating antibacterial agents, when the cell ruptures, additional bacteriophages are released, which can infect other bacterial cells. This cycle of infection and lysis enables bacteriophages to rapidly multiply at the site of infection, effectively eliminating specific bacterial populations. Their ability to self-replicate provides a long-term antibacterial impact, as new waves of phages continue to target and eradicate remaining dangerous bacteria, potentially providing a broader and long-lasting treatment to bacterial infections than traditional antibiotics 10 . Furthermore, 59 clinical studies completed between 2000 and 2021 were evaluated and discovered that 79% of 1,904 patients with chronic and drug-resistant infections improved after receiving phage treatment, while 87% of the target bacteria were eradicated in 1,461 cases 35 .
Mechanisms of action
Bacteriophages undergo a lytic cycle, which is a multi-step process that starts with the phage adhering to receptors on the bacterial cell surface 36 . This attachment is extremely precise, frequently requiring interactions between phage tail fibres and bacterial surface proteins or polysaccharides 34 . Once the phage has successfully attached, it injects its DNA into the host cell, causing the bacterial machinery to copy its genetic material and make phage proteins. During this stage, the bacterial cell's usual processes are disturbed as it is reprogrammed to form new phage particles 9 . As the number of phage particles inside the bacterium rises, the cell's structural integrity deteriorates. Finally, the bacterial cell lyses, or bursts, releasing a new generation of phages into the surrounding environment 1 . These freshly generated phages can then infect neighbouring bacterial cells, repeating the cycle and effectively lowering bacterial numbers 9 .
Figure 1: A diagram showing the different stages a bacteriophage undergoes during the lytic cycle 3 .
Applications in Food Safety
Meat and Poultry Processing: Phages can be used on raw meat and poultry to minimise infections such as Salmonella and E. coli. Studies have demonstrated that using phages during processing reduces bacterial levels significantly 12 . For example, a 90% reduction in Salmonella in chickens treated with a specific phage mixture was found 14 . The most prevalent phages employed in these applications are those that target Salmonella , Listeria , and E. coli . Actual phages employed include Felix O1 and SJ2 for Salmonella , P100 for Listeria monocytogenes , and T4 and T7 for E. coli 37 . Furthermore, phage cocktails, which include many phages, can be more effective than single-phage therapies. This is because they can target a wider spectrum of bacterial strains within a species, lowering the risk of bacterial resistance and giving a more thorough strategy to bacterial eradication 1 . Phage cocktails take advantage of the unique processes of many phages, increasing the overall efficacy of the therapy and assuring a more powerful reduction in bacterial contamination 2 .
Fresh Produce: Contaminated fresh vegetables are a common cause of foodborne illness. Phages can be sprayed on fruits and vegetables to kill surface germs, increasing shelf life, and ensuring safety 33 . In a study, the use of phages on cantaloupes and apples drastically reduced Listeria monocytogenes numbers 20 .
Dairy Products: Phages are used in cheese production to reduce spoilage bacteria, hence enhancing product quality and safety 12 . Bacteriophages have been employed successfully to treat lactic acid bacterial infections in cheese, resulting in a higher-quality product 5 . Phages like phiIPLA-RODI and phage P008 are unique to Lactococcus and Lactobacillus species 23 . These phages target spoilage bacteria, which may negatively affect cheese texture, flavour, and overall quality 8 .
In the case of cheese production, phages are added to milk or curds to eliminate unwanted bacteria that can outcompete or infect beneficial lactic acid bacteria. Phages contribute to the microbial ecosystem balance required for optimum cheese fermentation by lowering the population of spoilage bacteria 29 . This leads to a more uniform product with improved texture, flavour, and safety. Furthermore, phages can be utilised selectively to target certain spoilage organisms while preserving the beneficial bacteria required for cheese manufacturing, improving the overall quality and safety of the finished product 29 .
Seafood: Phages can lower infections in raw and undercooked fish, including Vibrio species 9 . A study found that phage spraying reduced Vibrio vulnificus levels in oysters by 99% 19 .
Figure 2 : An image of a bacteriophage-based tool, ListShield™, used to mitigate Listeria contamination in ready-to-eat foods using six naturally occurring bacteriophages, ListShield™ works by lysing Listeria bacteria without affecting food quality 16 .
Advantages of Using Bacteriophages
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Specificity: Unlike broad-spectrum antibiotics, phages target only specific bacteria, minimising disruption to beneficial microbiota 32 . This means that, although antibiotics can kill a wide variety of bacteria, including many that are helpful to our health, phages are highly selective, infecting only specific bacterial strains. Beneficial microbiota is the population of beneficial bacteria that reside in and on our bodies and play critical roles in digestion, immunological function, and overall health. Using phages that selectively target bad bacteria prevents the collateral damage that broad-spectrum antibiotics can do to these beneficial bacterial communities, preserving their positive benefits to our health 22 .
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Natural and Safe: Phages are naturally occurring and considered safe for human consumption by regulatory bodies like the United States Food and Drug Administration (FDA) 2 . Phages are non-harmful because they target and infect bacteria without hurting human cells. The body automatically breaks down and metabolises phages after they have completed their infection cycle and removed the target bacterium. This technique guarantees that phages do not accumulate or create harmful effects, which improves their safety profile 32 .
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Reducing Antibiotic Resistance: Phage therapy offers a different treatment option compared to antibiotics, helping combat the growing issue of antibiotic resistance 33 .
Unlike antibiotics, which frequently exert broad selected pressure that might lead to widespread antibiotic resistance, phages are very particular in their target bacteria, reducing overall selective pressure on bacterial populations 21 . This selectivity helps to sustain beneficial bacteria and decreases the possibility of acquiring resistant strains. However, it is crucial to remember that phage genomes are still not entirely known, and the topic of phage resistance requires further investigation 6 . Some bacteria can develop resistance to phages, and bacteriophages can transport resistance mechanisms between bacterial cells during infection. This means that, like antibiotics, phages have the potential to propagate resistance if not managed effectively 22 .
Using phage cocktails, which are mixtures of different phages, can help mitigate this risk. Phage cocktails target multiple bacterial strains and reduce the likelihood of resistance developing, as it is more difficult for bacteria to simultaneously develop resistance to several phages 39 . Despite this, the possibility of resistance remains, and ongoing research is necessary to fully understand and address these concerns.
Challenges and Considerations
Regulatory Hurdles: Regulatory approval for phage uses in food differs by area, with some needing rigorous testing to assure safety and efficacy 12 . For example, the European Food Safety Authority (EFSA) sets strict standards for innovative food additives, which might hinder the approval process. For a food additive to be authorised, the EFSA requires detailed information about its identity, manufacturing process, chemical composition, stability, and reactivity and destiny in foods. This includes specific safety data, such as its genotoxic potential and other toxicological facts essential to its safety 38 . Hages must meet strict criteria to protect human health. The EFSA's Panel on Food additions and Flavourings (FAF) conducts safety evaluations, reviewing both novel additions and any new uses of existing additives. This extensive review method protects consumer health by guaranteeing that phages and other food additives do not harm food safety or quality 38 .
Bacterial Resistance: Bacteria can develop resistance to both antibiotics and bacteriophages. It has been suggested that continued research and the development of phage combinations are necessary to prevent resistance 9 . Some researchers found that mixing numerous bacteriophages can reduce the probability of resistance 27 . This is because using a diverse cocktail of phages targets bacteria via various methods, making it more difficult for the bacteria to build resistance to all the phages in the mixture.
Public Perception: The acceptability of bacteriophages in food products is crucial. Educating the public about the safety and benefits of bacteriophages is critical for overcoming scepticism 33 . It was found that, while consumers are first sceptical, education dramatically boosts acceptability 26 . A variety of factors contribute to public scepticism of bacteriophages in food items, including a lack of information, safety concerns, issues about naturalness, and questions about efficacy 15 .
Many people are unfamiliar with bacteriophages and their significance in treating bacterial infections or improving food safety 31 . The concept of employing viruses, even good ones, is frequently misinterpreted, causing doubt 28 . Safety issues are also prominent, with some consumers concerned about the potential side effects or long-term health consequences of eating phage-treated foods 15 .
However, studies showed that educating consumers addressed the knowledge gaps in consumers by significantly improving the acceptance of phage-based treatments 25 . While bacteriophages exist naturally in the environment and the human gut, many consumers prefer raw and minimally processed meals 7 .
Furthermore, there is scepticism about bacteriophages' efficacy, especially in compared to known techniques like as antibiotics or chemical preservatives 7 . People may be sceptical that phages can effectively replace established ways for combating bacterial contamination, which could hinder the adoption of phage-based therapies and goods.
To address public concerns about bacteriophages, educational campaigns are essential. Providing clear, accessible information on how phages work and emphasizing that they are naturally occurring in our environment and bodies can help reduce apprehension 4 . Sharing scientific data, such as research showing that phage intake has no harmful health impacts, can help to establish trust. For example, regulatory agencies like as the FDA and EFSA have previously approved phage applications as safe, which might be mentioned to comfort customers 2 .Transparency in how corporations utilise phages, combined with labelling that emphasises their natural and tailored effect, might also appeal to health-conscious customers, encouraging greater acceptance 33 .
Phage Therapy in the UK
Phage therapy is gaining popularity in the UK; however, it is not yet widely available. It is generally used in clinical settings to treat antibiotic-resistant infections, particularly when other therapies fail. Furthermore, phage therapy in the UK is overseen by health agencies such as the EFSA and must adhere to strict regulatory criteria to ensure safety and efficacy. Clinical research and compassionate use situations are closely monitored. When it comes to research and development, the UK is heavily involved in phage research, with several organisations like biotechnology companies investigating its applications in health and food safety 24 . New opportunities include creating phage-based therapies for persistent bacterial diseases and employing phages to minimise foodborne pathogens 2 . The economic impact of phage therapy in the UK is expected to keep growing as antibiotic resistance becomes a more important concern. The global phage therapy market could generate hundreds of millions of pounds in revenue, driven by demand for innovative antimicrobial therapies and food safety solutions 17 .
Conclusion
Bacteriophages represent a possible approach for improving food safety by addressing the limitations of previous technologies and providing a natural, effective means of combating foodborne diseases. Continued research, regulatory support, and public education are critical to the widespread application of phage technology in the food business. These developments may make phage applications more practical and acceptable, potentially revolutionising both food safety and medical treatments.
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