H2020 PHAGOVET Project: A cost-effective solution for controlling Salmonella and Escherichia coli in poultry production
- Type Project
- Status Filled
- Execution 2018 -2022
- Assigned Budget 2.611.208,25 €
- Scope Europeo
- Main source of financing H2020
- Project website Proyecto PHAGOVET
Salmonella and Escherichia coli are the most common infectious pathogens in poultry. Antibiotics are widely used on farms to treat infections; however, their overuse has led to an increase in antimicrobial resistance in both animals and humans. To mitigate this effect, the EU-funded PHAGOVET project proposes cost-effective biocides and feed additives based on bacteriophages to target and eliminate bacteria.
It will be the first phage-based solution that naturally controls both bacteria in poultry production, while avoiding the side effects and residues associated with antibiotic use. This natural alternative to antibiotics will benefit EU poultry and egg production, one of the largest in the world.
During this period, to achieve the production of commercial batches of the phage cocktail, a new phage production company was subcontracted and produced different batches of the PhagoVet product used in the various tasks performed during this period. To do so, it was necessary to implement and provide the company with protocols related to the production of phage lysates, PCR detection of phages, and PCR detection of DNA from production strains, among others, to ensure that the product met EFSA requirements. In this regard, regarding the efficacy of the PhagoVet biocidal product, three different batches of the PhagoVet cocktail were tested in experiments conducted following standard regulations for the evaluation of the bactericidal activity of chemical disinfectants and antiseptics (biocides) used in the veterinary field on porous and non-porous surfaces. To this end, the regulations were adapted to the specific nature of bacteriophages.
The results demonstrated a significant reduction in Salmonella concentration on liquid and non-porous surfaces under two different soiling conditions, achieving the log10 reduction required by the relevant regulations. A low effect was observed on porous surfaces. Regarding the "Evaluation of the zootechnical feed additive PhagoVet," the efficacy and tolerance of the zootechnical feed additive PhagoVet against Salmonella were analyzed through in vivo trials on broiler and laying hen farms in two different geographical locations in Europe. Ten independent animal trials were conducted: two concept trials, seven efficacy trials, and one safety trial, carried out in accordance with Regulation (EC) 1831/2003. Two different Salmonella serovars were used for infection, and different infection conditions and administration of the phage cocktail in drinking water were evaluated. Overall, the results obtained in some trials demonstrated the efficacy of PhagoVet treatment in broiler chickens. Significant differences were observed in Salmonella counts on tights at the end of the trial at 35 days, which had a positive impact on zootechnical performance.
Considerable effort was also devoted to preparing dossiers for the evaluation of the food additive and biocide Phagovet by the relevant agencies. To this end, various studies were conducted, including the characterization and sequencing of bacteriophages and Salmonella-producing strains, as well as other studies related to product safety, including consumer and user safety.
Regarding the evaluation of PhagoVet as a biocide, the competent authorities of nearly 25 EU Member States were contacted to undertake the risk assessment of PHAGOVET. However, most declined the request, citing excessive workload and a lack of experience in bacteriophage evaluation. We will continue working on preparing the registration dossier and seeking an available authority for review. The dossier for the PhagoVet feed additive is under preparation and is expected to be submitted for evaluation in the short term. Finally, the final marketing plan has been designed, focusing on the development of the zootechnical feed additive and biocide for the control of Salmonella. The project also contemplated the development of a feed additive to control the presence of E. coli in poultry production.
Due to budgetary and regulatory constraints (after the registration pathway for the E. coli phage solution PHAGOVET as a food additive was not suitable or accepted by EU authorities, requiring registration as a veterinary product), work was focused on work packages 1, 2 and 3, with the aim of gathering knowledge and data to develop a prototype product and support a possible registration of the E. coli phage solution as a veterinary product in the future.
A total of 44 E. coli phages were isolated and functionally and morphologically characterized, of which 32 were found to be lysogenic or possess toxin or antibiotic resistance genes, rendering them unsuitable for therapy. The remaining 12 would be suitable for integrating a cocktail formulation. However, the lytic spectra of these phages were too narrow to cover the genetic diversity of E. coli isolated in the field, making it difficult to produce a fixed cocktail formulation that would function as a broad-spectrum solution. For E. coli treatment, we found that customized formulations designed to kill the bacteria actually infecting the animals would be the best treatment option.
The Phagovet project is designed to meet market demand for a safer and more reliable solution for controlling Salmonella infection in poultry farms. Salmonellosis is currently considered the leading bacterial infection in the poultry sector, with significant economic impact worldwide. Furthermore, among other causes, the overuse of antibiotics in livestock farming has led to an increase in antimicrobial resistance, a serious problem for human health today.
In response to this unmet need, PhagoVet offers a cost-effective alternative to antibiotics against Salmonella. PhagoVet consists of a biocide and feed additive technology based on selected bacteriophages capable of eliminating target bacteria. PhagoVet will be the first phage-based solution to naturally and effectively control bacteria in poultry production, avoiding the side effects and residues associated with antibiotic use. It will reduce Salmonella infections by 20%. Therefore, PhagoVet offers a promising and effective control measure for a problem of concern to both poultry farmers and human health.
The Phagovet project is designed to meet market demand for a safer and more reliable solution for controlling Salmonella and E. coli infections in poultry farms. With more than 40,000 poultry farms, the European Union (EU-28) is the world's fourth-largest producer of poultry meat (13.1 million tonnes, 2014) and the second-largest producer of eggs (>11 million tonnes, 2014).
The European poultry industry employs 302,000 people across Europe and has an annual turnover of €30 billion, making it of significant economic importance. To date, avian colibacillosis and salmonellosis are considered the main bacterial infections in the poultry sector, with a significant economic impact worldwide. Furthermore, the EFSA estimated the global economic burden of human salmonellosis at €3 billion per year. Finally, the overuse of antibiotics in agriculture has led to an increase in antimicrobial resistance. 700,000 people die annually from drug-resistant infections, and this number is estimated to rise to 10 million by 2050. In response to this unmet need, Phagovet proposes a cost-effective alternative to antibiotics against Salmonella and E. coli. Phagovet consists of a biocide and two technological feed additives based on selected bacteriophages capable of killing target bacteria. Phagovet will be the first phage-based solution that will naturally and effectively control both bacteria in poultry production, while avoiding the side effects and residues associated with antibiotic use. It will reduce Salmonella infections by 20% and reduce the use of antibiotics against E. coli by 50%.
Phagovet therefore provides a promising and effective control measure for a problem of concern to poultry farmers and human health. The successful market launch of Phagovet will allow the Consortium members to consolidate their position in the Animal Health, Food Safety, and Environmental Control markets and market the product worldwide, achieving revenues of €17.76 million by the end of 2026.
Escherichia coli and Salmonella are the scourge of the poultry industry. An alternative to antibiotic overuse could be bacteriophages. PHAGOVET is testing them. The European poultry sector is of utmost importance to the economy. With more than 40,000 poultry farms, 12 million tons of meat, and around 10 million tons of eggs produced, the annual turnover in Europe amounts to €30 billion. Avian colibacillosis and salmonellosis are the main bacterial infections in the poultry sector, with a huge economic impact. The European Food Safety Authority estimates the global economic burden of human salmonellosis at €3 billion annually. The overuse of antibiotics represents another major challenge for controlling these bacteria, along with the ever-present health threat of antimicrobial resistance. EU-funded PHAGOVET has developed a cost-effective alternative to control both microbes. Phages and antiseptic cocktail “Bacteriophages, or phages, are viruses that specifically infect and kill bacteria without negative effects on human or animal cells,” explains Daniela Silva, project coordinator.
During their life cycle, phages bind to and invade target bacteria. “Phage infection is an extremely specific and selective process, as phage structures must match strain-specific variants of bacterial receptors,” Silva explains. However, phage specificity is a double-edged sword, as one type of phage cannot wipe out all bacterial strains present. PHAGOVET’s answer to this is a phage cocktail, the biocide PHAGOVET, blended to target a spectrum of Salmonella strains. To further increase the product’s efficacy, “technological feed additives” containing bacteriophages against E. coli and Salmonella are applied to feed or drinking water. Triumphant trials do not come without tribulations. Another aspect the team took into account was the different mutation rates of the bacteria in question. Due to E. coli's high mutation rate, the use of phage-based products presents a greater challenge compared to Salmonella, which is much more genetically stable than E. coli. While a cocktail with a fixed formulation for immediate action may be available, the laboratory must always isolate the bacteria and test them against the available phage library.
If necessary, the cocktail formulation must be tailored to each specific situation,” says Silva. The team has adapted to this limitation with a large phage library and very well-characterized phages. “Then, once the E. coli is identified, the best combination of phages can be mixed and administered to the animals to obtain the most effective treatment,” concludes Silva. Studies show a significant reduction in Salmonella colonization two weeks after infection in animals treated with the zootechnical additive PHAGOVET. “The most promising results concern the shedding of Salmonella into the environment by Salmonella-infected birds,” notes Silva. The PHAGOVET-treated group showed almost no Salmonella shedding into the environment compared to the control group, and also showed statistically lower Salmonella counts in the cecum of PHAGOVET-treated birds during the first two weeks after infection.
The results of the PHAGOVET biocide are also positive: a significant reduction in Salmonella contamination was observed on the surfaces where it was applied. Forging a future for phage-based products in Europe “The PHAGOVET project offers a cost-effective and effective solution to combat major bacterial pathogens in poultry through a combination of phage-based biocides and technological feed additives,” Silva summarizes. Currently, there is no regulatory framework that allows for the inclusion of bacteriophages with their specificities. However, the project will continue to collect as much data as possible in order to submit a comprehensive application to the EU authorities for a registration framework for bacteriophage products.
Antibiotics have been routinely used in poultry to promote animal growth or prevent disease outbreaks. Their overuse has led to drug-resistant strains, increasing antimicrobial resistance, a major problem in both animal and human medicine. In 2006, the EU banned the use of antibiotics as growth promoters and will implement new restrictive legislation in 2018. In 2017, the US Food and Drug Administration (FDA) limited the use of antibiotics to the treatment or prevention of diseases prescribed by a veterinarian.
Therefore, the need for alternatives to the use of antibiotics in intensive livestock farming is now imperative. The PhagoVet solution is based on patented bacteriophage technology, owned by a consortium partner, combined with years of laboratory research and expertise in the field of microbiology, to produce the first bacteriophage-based product for the effective control of Salmonella in poultry farms.
The project will tap into the global animal health market, opening up the European and global phage market, not only strengthening our industrial partners and boosting research capacity, but also having a long-term impact on the EU economy and employment. Furthermore, our goal is to provide poultry farmers with an efficient, cost-effective, easy-to-use, and safe tool to combat Salmonella as an alternative to antibiotics. We are convinced that bacteriophages are the answer to this health and safety issue, and Phagovet will represent a step towards an effective solution.
- ALS LIFE SCIENCES PORTUAL S.A (CONTROLVET)
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