A new research collaboration is aiming to tackle one of the U.K. shellfish sector’s most persistent issues – larval mortality in hatcheries.
With a focus on developing practical, scalable tools to improve larval survival rates, the project includes U.K. biotech company Esox Biologics, the University of Glasgow, and the University of Leicester’s phage research center, with industry input from the Association of Scottish Shellfish Growers.
In an attempt to solve their mortality issues, U.K. hatcheries have often turned toward antibiotics, but these operations have come under increasing pressure to reduce their antibiotic use due to both regulatory constraints and declining efficacy.
Phages – naturally occurring viruses that target specific bacteria without disrupting broader microbial communities – have been identified as a promising alternative to antibiotics, particularly in sensitive hatchery environments.
Central to the new project is Esox’s “Detect” platform, which uses metagenomic sequencing to map bacterial and phage communities in hatchery environments.
Esox Biologics Managing Director Matthew Pope explained that translating that data into real-world treatments requires researchers to identify the specific pathogens responsible for mortality events.
“To develop a real-world phage therapy, first we must identify the bacteria associated with shellfish mortality. Then, we must isolate this bacterium, at which point we may begin prospecting for phage communities that infect it,” he told SeafoodSource.
Pope said traditional microbiological methods are a limiting factor to progress, so his company, under its Detect platform, uses genomic data as a reference point to guide the process.
“Bacterial isolation requires culture, [which is] a targeted and often unsuccessful approach as it is estimated that fewer than 1 percent of all microbes may be grown in isolation in laboratories,” he said. “Our Detect platform is culture-independent and reveals genomic sequences of the bacteria and phages present in water and tissue samples when shellfish mortalities occur. We can use these genomic datasets as our objective truth, verifying if the bacteria that we culture are the same strains we know to be associated with mortality.”
While phages offer a targeted approach to disease control, that specificity also presents a major scaling challenge.
“This is one of the greatest challenges phage therapies face,” Pope said. “If the bacterial pathogens affecting livestock differ between production sites, new phages must be isolated and prepared for each target pathogen.”
Besides scaling, technological barriers to adoption of phage-based solutions in shellfish hatcheries also exist, according to Pope.
“We know phage biocontrol solutions work in research environments, but a technological challenge is producing affordable titers at scale, dense enough to positively modulate the microbiome by removing the harmful shellfish pathogens,” he said.
Dilution effects in aquatic environments present an additional complication, he explained.
“Phages may easily be diluted within the milieu of microbes present in marine and freshwater, particularly flow through production systems, and we must first validate how many phages are required per unit of water to have a positive impact,” he said.
Additionally, even if all of the challenges are addressed, regulatory approval must be secured.
“For aquaculture in the U.K., a phage-based biocontrol product must first gain approval from the Veterinary Medicines Directorate (VMD),” Pope said.
Phage applications in aquaculture are not new, with multiple research groups exploring their potential as antibiotic alternatives, but Pope said that Esox’s role is differentiated by its focus on data generation rather than product development.
“Esox Biologics does not develop phage-based products; instead, we collect the genomic microbiome data necessary to inform phage product development,” he said. “We have the largest aquatic microbiome database in the world with which users can explore phage genomes within.”
If successful, even modest improvements in larval survival could have meaningful economic implications for producers.
“A 10 percent survival increase in research systems would be a great starting point, assuming we successfully identify a bacterial shellfish pathogen, isolate a corresponding phage, and use it for biocontrol,” Pope said.
Pointing out that demand for shellfish already exceeds supply in the U.K., such gains would translate directly into higher output.
“If we assume a hatchery’s survival rates yield [an] equivalent number of adults harvested, a 10 percent increase in juvenile survival would directly benefit producers through increased sales and reduced operational costs,” Pope said.
The commercial upside is echoed by project partners, with Martin Llewellyn of the University of Glasgow stating that improving larval survival “would unlock substantial growth and reverse recent declines in U.K. shellfish production.”