Bacteriophages: A Tool for Sustainability
This is part 2 of my phages series. Part 1 covered some of the medical uses. Here, I go over some uses in the food industry, water treatment facilities, and environmental uses.
Bacteriophages (phages for short) are viruses that specifically infect bacteria. They’re the most abundant life form on the planet with an estimated 10^31 of them, more than all other organisms combined. They have fascinated researchers since they were discovered over a century ago. These unimaginably tiny entities hijack bacterial machinery to eliminate harmful bacteria with great precision which makes them a great, multipurpose tool.
In the first part of this series (Phages Part 1: History and Medical Uses) we looked at what phages are, their history, and their medical applications like helping in the fight against antibiotic resistance. However, their therapeutic potential is only the tip of the iceberg and goes far beyond the hospital or clinical uses.
In this short part 2, we will look at the non-medical applications of phages. These include addressing challenges in food safety, environmental sustainability, crop disease, bacterial contamination in water sources, and more. Phages are looking like a viable and innovative approach to solving different problems in many fields. Let’s get into it!
Food Safety
Phages have been extensively studies for their safety in food applications. Regulatory agencies like the U.S. FDA and the European Food Safety Authority have approved phages that are non-toxic to humans, animals, or plants to be used in food production. Their ability to specifically target harmful bacteria without impacting beneficial microbes makes them a safe and precise tool for reducing bacterial contamination in food products 1,2.
Since foodborne illnesses from pathogens like Listeria monocytogenes, Salmonella enterica, and Escherichia coli are still significant public health concerns, but phages are emerging as a promising solution to enhancing food safety through their specificity in targeting these bacterial pathogens 1,3. Several phage based products are commercially available and have been approved for applications on meats, fresh produce and ready to eat foods 2. These include a line of products from the company Intralytix, including ListShield, SalmoFresh and EcoShield. Their ability to attack the harmful bacteria while keeping the beneficial microbes intact aligns with the growing demand for natural and sustainable food safety methods that reduce our reliance on chemical preservatives and antibiotics4. Phage-based food packagings are also being developed to hopefully extend shelf life, one being produced by NexaBiome that demonstrated an ability to extend shelf life of salads by 50% when phages are attached to the packaging itself5.
Biofilm Control and Wastewater Treatment
Two major problems in wastewater systems are bacterial overgrowth and biofilm formation. Biofilms are dense communities of microbes that attach to surfaces, encasing themselves in a protective matrix, making them resistant to chemical disinfectants and physical cleaning methods. These structures clog pipes reducing system efficiency. They can also be the home to harmful pathogens that can contaminate the water supply. Phages are being looked into as a sustainable solution to these challenges, specifically targeting bacterial species like Salmonella, Vibrio, Legionella, and E. coli 6,7. Phages are showing to be a solution to this bacterial overgrowth and biofilm related issues. Their ability to penetrate the biofilms and degrade the matrix they’re composed of exposes the bacteria to the phages allowing for infection of those bacterial species8. This specific targeting of harmful bacteria allows for the improvement of wastewater treatment efficiency without impacting the beneficial microbes that help with bioremediation processes9. In one study, phages successfully reduced biofilms formed by Psuedomonas aeruginosa in industrial water systems, improving flow efficiency and reducing further contamination risk8.
Phages are also able to serve as a reliable indicator of fecal contamination in water sources. Detecting phages specific to bacteria associated with human or animal waste lets researchers identify pollution sources, such as agricultural runoff or wastewater leakages, more effectively than the use of traditional bacterial testing methods allow for7,10. This combined with resilience to environmental stressors like UV light or temperature makes them all the better as water quality markers6.
Water Desalination Systems
Biofilm formation has proved to be a significant challenge in water desalination systems, since biofilms clog the filtration membranes, reduce system efficiency, and can cause malfunctions. Recent studies have been looking at phages as an alternative to chemical and physical treatments for biofilm mitigation in seawater applications. Research in the area is still in its infancy, but phages applied to biofilm membranes have been shown to significantly reduce the abundance of bacterial species. Combined with citric acid, phage treatments improved membrane performance through reducing buildup by almost 50% compared to citric acid use alone10.
Petroleum Industry Applications
In the petroleum industry sulfate reducing bacteria (SRBs), like those in the genus Desulfovibrio, cause some significant problems. These bacteria produce hydrogen sulfide, a toxic gas that corrodes pipelines and contaminates oil reserves, reducing the overall quality of petroleum products. Hydrogen sulfide can also oxidize into sulfuric acid, exacerbating the damages to infrastructure 6. Work is being done to identify the specific prophage genes that encode for the enzymes that target these bacteria and work has been done showing phages can inhibit biofilm formation from common bacteria to oil pipeline systems13.
Soil Health and Agriculture
Phages have a pivotal role in the regulation of bacterial populations in soil, as they influence nutrient cycling and microbial community dynamics6. In the rhizosphere (fancy word for soil zone near the roots), phages mediate interactions between the plant roots and beneficial bacteria, allowing for increased nutrient uptake and crop growth. They also act as biocontrol agents that can target pathogens like Dickeya solani, the cause of blackleg and rot in potatoes, and Pseudomonas savastanoi pv. glycinea, the bacteria responsible for spotting in soybeans, grapes, and citrus fruits5,6. EPA approved products like AgriPhage and XylPhi-PD have demonstrated commercial viability for phages in agriculture. AgriPhage is used to treat bacterial infection in fruits and vegetables, including Fire Blight in apples and pears caused by Erwinia amylovora. XylPhi-PD is used in grapevines to target Xyellla fastidiosa, a bacteria that causes the grapevine to weaken and die off5.
Pollinator Health
Pollinators, honeybees in particular, are essential for global agriculture as they contribute to the pollination of 75% of plant species and 35% of our food supply11. However, bee populations have been in decline due to a variety of factors like habitat loss and pesticide use, but one of the most devastating effects, American Foulbrood (AFB) is caused by the bacteria Paenibacillus larvae. Current treatments for AFB are severely limited. Antibiotics can be effective, but they leave residues in the honey impacting quality and safety. This leaves burning the infected hives as the only option, one that is both drastic and unsustainable. Phages have been proposed and tested as an alternative. Phages and their enzymes have been identified that are able to break down bacterial cell walls and are highly effective against P. larvae. This could help control AFB infections without harm to the bees or leaving a harmful residue in the honey5,12.
Conclusion
Phages are proving to be an excellent tool for fighting antibiotic resistance, safeguarding our food supply, improving wastewater treatment, and many more applications will likely be found for these entities. Even though many of those are still up and coming, the research is promising and commercial successes of the phage based biocontrol products in agriculture and food safety show just how feasible broader adoption is. However, some significant challenges need to be addressed. Scaling production, addressing regulatory barriers, and working on ecological safety measures will help unlock the true potential of phages. I think phages will have a fascinating role in the world to come and this area is worth following!
Citations
1. Garvey M. Bacteriophages and Food Production: Biocontrol and Bio-Preservation Options for Food Safety. Antibiotics. 2022;11(10):1324. doi:10.3390/antibiotics11101324
2. Wagh RV, Priyadarshi R, Rhim JW. Novel Bacteriophage-Based Food Packaging: An Innovative Food Safety Approach. Coatings. 2023;13(3):609. doi:10.3390/coatings13030609
3. Imran A, Shehzadi U, Islam F, et al. Bacteriophages and food safety: An updated overview. Food Sci Nutr. 2023;11(7):3621-3630. doi:10.1002/fsn3.3360
4. Ranveer SA, Dasriya V, Ahmad MF, et al. Positive and negative aspects of bacteriophages and their immense role in the food chain. Npj Sci Food. 2024;8(1):1. doi:10.1038/s41538-023-00245-8
5. Siyanbola KF, Ejiohuo O, Ade-adekunle OA, et al. Bacteriophages: sustainable and effective solution for climate-resilient agriculture. Sustain Microbiol. 2024;1(1):qvae025. doi:10.1093/sumbio/qvae025
6. Batinovic S, Wassef F, Knowler SA, et al. Bacteriophages in Natural and Artificial Environments. Pathogens. 2019;8(3):100. doi:10.3390/pathogens8030100
7. Rogovski P, Cadamuro RD, da Silva R, et al. Uses of Bacteriophages as Bacterial Control Tools and Environmental Safety Indicators. Front Microbiol. 2021;12:793135. doi:10.3389/fmicb.2021.793135
8. Czajkowski R, Jackson RW, Lindow SE. Editorial: Environmental Bacteriophages: From Biological Control Applications to Directed Bacterial Evolution. Front Microbiol. 2019;10. doi:10.3389/fmicb.2019.01830
9. Reyneke B, Havenga B, Waso-Reyneke M, Khan S, Khan W. Benefits and Challenges of Applying Bacteriophage Biocontrol in the Consumer Water Cycle. Microorganisms. 2024;12(6):1163. doi:10.3390/microorganisms12061163
10. Scarascia G, Yap SA, Kaksonen AH, Hong PY. Bacteriophage Infectivity Against Pseudomonas aeruginosa in Saline Conditions. Front Microbiol. 2018;9. doi:10.3389/fmicb.2018.00875
11. Protecting Pollinators Critical to Food Production | NIFA. June 10, 2022. Accessed January 18, 2025. https://www.nifa.usda.gov/about-nifa/blogs/protecting-pollinators-critical-food-production
12. Sieiro C, Areal-Hermida L, Pichardo-Gallardo Á, et al. A Hundred Years of Bacteriophages: Can Phages Replace Antibiotics in Agriculture and Aquaculture? Antibiotics. 2020;9(8):493. doi:10.3390/antibiotics9080493
13. Crispim JS, Dias RS, Vidigal PMP, et al. Screening and characterization of prophages in Desulfovibrio genomes. Sci Rep. 2018;8(1):9273. doi:10.1038/s41598-018-27423-z
14. Ye M, Sun M, Huang D, et al. A review of bacteriophage therapy for pathogenic bacteria inactivation in the soil environment. Environment International. 2019;129:488-496. doi:10.1016/j.envint.2019.05.062