Prosjektnummer
901707
Genomic epidemiology and Phage-based Prevention of salmon associated Pasteurella (GP3)
Background
Pasteurella, the causative agent of pasteurellosis, is an increasingly emerging threat for farmed Norwegian salmon, and despite its implications and impact on fish stocks, little is known about this infectious agent. Antibiotic treatments are generally discouraged, vaccine development is still in its infancy and no specific effective treatments currently exist.
An obvious, targeted and timely approach to remove Pasteurella from salmon is to utilise bacteriophages the natural predators of bacteria. Bacteriophages, or phages for short, are viruses that specifically infect and kill bacteria without infecting, or further impacting animal cells. Each phage-type is able to infect and kill a narrow range of bacterial strains, which makes them suitable for development into highly precise antimicrobials. They can be applied to the water directly to kill bacteria and can be thought of as a unique ‘live’ antibacterial, to bridge the line between antibiotics and vaccines, making antimicrobial therapy more targeted and preventing problems associated with antibiotic resistance. Unlike vaccines, phages can both remove disease from fish and reduce disease spread within the wider environment lowering the chances for wild fish to be infected. The phage concentration in the environment is self-regulated as a phage cannot be active when there is no host to infect and its ability to strictly eliminate the pathogen population without affecting any other commensal microflora, makes them very promising disease control agents.
Phages have been successfully used to remove undesirable bacteria both in medicine, agriculture and other industries. In aquaculture, phage therapy is a particularly attractive option as applying in liquid conditions suits the natural biology of phages, increasing their ability to find and kill their target bacterial hosts. Phages have been used to remove pathogenic bacteria from fish and seafood including shrimp, oysters, lobsters, sea cucumbers, salmon and cod. Data consistently demonstrate that phages cause a significant reduction in pathogen load whilst having minimal impact on the environment.
An obvious, targeted and timely approach to remove Pasteurella from salmon is to utilise bacteriophages the natural predators of bacteria. Bacteriophages, or phages for short, are viruses that specifically infect and kill bacteria without infecting, or further impacting animal cells. Each phage-type is able to infect and kill a narrow range of bacterial strains, which makes them suitable for development into highly precise antimicrobials. They can be applied to the water directly to kill bacteria and can be thought of as a unique ‘live’ antibacterial, to bridge the line between antibiotics and vaccines, making antimicrobial therapy more targeted and preventing problems associated with antibiotic resistance. Unlike vaccines, phages can both remove disease from fish and reduce disease spread within the wider environment lowering the chances for wild fish to be infected. The phage concentration in the environment is self-regulated as a phage cannot be active when there is no host to infect and its ability to strictly eliminate the pathogen population without affecting any other commensal microflora, makes them very promising disease control agents.
Phages have been successfully used to remove undesirable bacteria both in medicine, agriculture and other industries. In aquaculture, phage therapy is a particularly attractive option as applying in liquid conditions suits the natural biology of phages, increasing their ability to find and kill their target bacterial hosts. Phages have been used to remove pathogenic bacteria from fish and seafood including shrimp, oysters, lobsters, sea cucumbers, salmon and cod. Data consistently demonstrate that phages cause a significant reduction in pathogen load whilst having minimal impact on the environment.
Objectives
Main objective
To develop a targeted phage therapy solution to prevent and control Pasteurella skyensis and other strains associated with pasteurellosis in Atlantic salmon farms.
Sub-objectives
• To identify the diversity and distribution of Pasteurella in both Norwegian and Scottish farmed salmon.
• To identify and isolate phages that attack and kill salmon associated Pasteurella strains.
• To determine the safety, efficacy and formulation for these phages.
• To produce safety documentation according to the Norwegian Food Authority (NoFA) requirements so that real-life field trials can be allowed. Field trials will be carried out to develop easy-to-use administration methods and provide efficacy documentation for the use of phage-based solutions against Pasteurella.
Main objective
To develop a targeted phage therapy solution to prevent and control Pasteurella skyensis and other strains associated with pasteurellosis in Atlantic salmon farms.
Sub-objectives
• To identify the diversity and distribution of Pasteurella in both Norwegian and Scottish farmed salmon.
• To identify and isolate phages that attack and kill salmon associated Pasteurella strains.
• To determine the safety, efficacy and formulation for these phages.
• To produce safety documentation according to the Norwegian Food Authority (NoFA) requirements so that real-life field trials can be allowed. Field trials will be carried out to develop easy-to-use administration methods and provide efficacy documentation for the use of phage-based solutions against Pasteurella.
Expected project impact
It is anticipated that the proposed bacteriophage-based studies for salmon Pasteurella control will provide the data needed for the subsequent development of a novel product that will ultimately improve salmon health and prevent stocks from being decimated by this pernicious pathogen.
It is anticipated that the proposed bacteriophage-based studies for salmon Pasteurella control will provide the data needed for the subsequent development of a novel product that will ultimately improve salmon health and prevent stocks from being decimated by this pernicious pathogen.
Anticipated principal outputs of industrial relevance are:
1. An extensive understanding of the Pasteurella diversity, early warning markers for disease outbreaks and improved scientific foundation for advising biosecurity and hygiene measures
2. Identification and isolation of a set of bacteriophages that target Pasteurella with the aim of reducing infestations without harming the commensal microbiota.
Project design and implementation
An international consortium of complementary resources and expertise will conduct this research through the following five work packages (WP’s):
WP 1: Sample collection
In a two-step procedure, samples will be collected from salmon, lumpfish and the environment (water, sediments, wellboats, and cages) from 10 to 12 different production sites in Norway and Scotland respectively, via the collaborator Lerøy Seafood Group, ACD Pharma, STIM, and University of Stirling.
WP 2: Pasteurella diversity and virulence studies
The landscape of Pasteurella diversity and geography will be established, to serve as the search space for understanding the extent of the problem and as a means to specifically identify phages that target Pasteurella associated with Atlantic salmon.
WP 3: Phage isolation and characterisation
In this work package, lytic phages targeting Atlantic salmon associated strains of Pasteurella that are known to be problematic in Norway and Scotland will be isolated and characterised. Phages will be isolated from water, cage/wellboat scrapings, sediments, salmon and lumpfish skin, gut and gill microbiomes and sequenced in order to determine molecular diversity and to identify best-suited phage ‘types’ for further development.
WP 4: Phage Formulation
In order to create a product for widespread usage within the aquaculture industry, spray drying parameters will be optimised to improve their stability of use and in order to prevent dependency on a cold chain when using the product.
WP 5: Safety and efficacy trials
Candidate phage cocktails which pass initial in vitro testing will be subject to safety and efficacy trials. Trials will initially be done in small scale (lab) settings, and gradually progress to large scale field trials carried out between partners Lerøy and ACD.
WP 1: Sample collection
In a two-step procedure, samples will be collected from salmon, lumpfish and the environment (water, sediments, wellboats, and cages) from 10 to 12 different production sites in Norway and Scotland respectively, via the collaborator Lerøy Seafood Group, ACD Pharma, STIM, and University of Stirling.
WP 2: Pasteurella diversity and virulence studies
The landscape of Pasteurella diversity and geography will be established, to serve as the search space for understanding the extent of the problem and as a means to specifically identify phages that target Pasteurella associated with Atlantic salmon.
WP 3: Phage isolation and characterisation
In this work package, lytic phages targeting Atlantic salmon associated strains of Pasteurella that are known to be problematic in Norway and Scotland will be isolated and characterised. Phages will be isolated from water, cage/wellboat scrapings, sediments, salmon and lumpfish skin, gut and gill microbiomes and sequenced in order to determine molecular diversity and to identify best-suited phage ‘types’ for further development.
WP 4: Phage Formulation
In order to create a product for widespread usage within the aquaculture industry, spray drying parameters will be optimised to improve their stability of use and in order to prevent dependency on a cold chain when using the product.
WP 5: Safety and efficacy trials
Candidate phage cocktails which pass initial in vitro testing will be subject to safety and efficacy trials. Trials will initially be done in small scale (lab) settings, and gradually progress to large scale field trials carried out between partners Lerøy and ACD.
Dissemination of project results
The project group will implement a dissemination strategy designed to maximise timely sharing and publication of research results. The project will engage a communication company (Scientifica) to produce video material and targeted messages about the project and project findings. This content will be distributed through all the relevant communication channels available within the consortium, as well as through social media. Information about the project and project findings will also be published as popular scientific summary articles in relevant aquaculture news media such as Kyst.no and Intrafish. This way the project plan to also reach a range of stakeholders outside the scientific community.
The project group will implement a dissemination strategy designed to maximise timely sharing and publication of research results. The project will engage a communication company (Scientifica) to produce video material and targeted messages about the project and project findings. This content will be distributed through all the relevant communication channels available within the consortium, as well as through social media. Information about the project and project findings will also be published as popular scientific summary articles in relevant aquaculture news media such as Kyst.no and Intrafish. This way the project plan to also reach a range of stakeholders outside the scientific community.
Prosjektnyheter
01.07.2021
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