Prosjektnummer
Genomic epidemiology and Phage-based Prevention of salmon associated Pasteurella (GP3)
Hovedmålet med GP3-prosjektet var å utvikle en målrettet fagterapiløsning for å forebygge og kontrollere pasteurellose, forårsaket av Pasteurella skyensis og relaterte stammer, i atlantisk lakseoppdrett. Gjennomføringen inkluderte omfattende prøvetaking i Norge og Skottland. Prosjektet fastslo at gjelleslim er det optimale stedet for å gjenopprette Pasteurella-DNA. En stor utfordring var at bakterien (nå anerkjent som Phocoenobacter) har mange anti-fagforsvarssystemer, som vanskeliggjorde tradisjonell fagisolering. Prosjektet lyktes i å pivotere til å utvikle Endolysin-terapi. Endolysin-kandidater ble identifisert, klonet og uttrykt. Viktigst er at lysater som inneholder uttrykte endolysiner (PE4/PE5) viste tydelig bevis på bakteriell drap (oppklaring) i punkttester mot mål stammene, noe som bekrefter prinsippet for endolysin-terapi. Denne validerte tilnærmingen gir et definert produkt med regulatoriske fordeler.
Pasteurella er svært god til å forsvare seg mot bakteriofager
Målet med prosjektet var å undersøke om pasteurellose kunne bekjempes ved hjelp av bakteriofager – virus som angriper og dreper bakterier. Mange bakteriesykdommer kan i prinsippet kontrolleres ved å tilføre store mengder slike virus. Forsøkene viste imidlertid at Pasteurella har et uvanlig effektivt forsvar mot bakteriofager, noe som gjør fagterapi svært utfordrende. Det sterke forsvarssystemet tyder samtidig på at bakterien gjennom evolusjonen har vært utsatt for betydelig press fra bakteriofager i naturen.
Prosjektet avdekket også at endolysiner – enzymer som kan bryte ned bakterieceller – kan være et alternativ i bekjempelsen av pasteurellose. Hvorvidt en slik behandling vil være praktisk og kostnadseffektiv under kommersielle forhold, gjenstår imidlertid å undersøke.
Når det gjelder diagnostikk, viste prosjektet at svaberprøver fra gjellene er den mest effektive metoden for å påvise bakterien. Dette funnet kan bidra til å forbedre prøvetaking og diagnostikk av sykdommen fremover.
Som en liten kuriositet har bakteriene bak pasteurellose nylig skiftet navn. Både Pasteurella atlantica og P. skyensis er nå omklassifisert til slekten Phocoenobacter. Sykdomsnavnet pasteurellose vil likevel trolig leve videre i lang tid.
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University of Copenhagen (UCPH).22.mai.2026. Prof. Thomas Sicheritz-Pontén
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.
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.
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.
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.
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.
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University of Copenhagen (UCPH).22.mai.2026. Prof. Thomas Sicheritz-Pontén