Much like humans during the holidays, fish seldom catch just one cold at a time. Yet much of what scientists know about fish health has been learned by studying pathogens one by one. Fish scientists at Auburn University and the USDA are challenging that approach through ongoing research on coinfection—cases where multiple pathogens infect a fish at once.
“Coinfections are bad,” deadpanned Benjamin LaFrentz, a molecular biologist at the USDA’s Agricultural Research Service. “Most studies are conducted on a single pathogen, which isn’t reality. In the real world, it’s never just one thing.”
Since 2021, the collaborative team has studied how combinations of bacterial and viral pathogens combine to attack warmwater fish, such as catfish, tilapia and largemouth bass. Their work seeks to understand not only whether coinfection worsens disease outcomes but also how and why.
Much of the team’s work centers on how coinfection doesn’t simply add additional risk. In most cases, it amplifies it, leading to increased likelihood of death for fish.
“When we add low doses of two pathogens, oftentimes we will see higher mortality than a higher dose of a single pathogen,” said Tim Bruce, assistant professor at the School of Fisheries, Aquaculture & Aquatic Sciences. “So, there are some weird synergies going on here.”
Those synergies explain why disease outbreaks in aquaculture ponds can be severe, unpredictable and difficult to manage. Farmers need answers on what to treat first, and whether current strategies still work when multiple pathogens are present.
“If I have two pathogens here, and they’re working in unison somehow on these fish, which one do I treat first? Do I treat A, or do I treat B?” said Bruce. “Sometimes if we treat A before B, we will get a different mortality pattern than B before A.”
Historically, coinfection research in aquaculture has been limited in scope. Much of the existing body of knowledge in catfish has focused on interactions between parasites and bacteria, leaving a knowledge gap in how bacteria interact with other bacteria or with viruses.
“Prior to our work, most coinfection studies in catfish have been parasite-bacteria, but not bacteria-bacteria or virus-bacteria,” said LaFrentz. “So, that was a gap.”
To better understand the interaction between fish and multiple diseases, the team uses cutting-edge genetic research. First, they study the gene expression of immune tissue from infected fish. By extracting messenger RNA, which tells the fish’s immune system how to respond to disease, they can measure which genes are “turned on” or “turned off.” This method allows them to see how strongly the immune system is responding, which immune pathways are activated and whether coinfection triggers a different response than a single pathogen. By treating coinfection not as more disease, but, rather, as a different disease, the method helps to explain why fish sometimes die faster or at higher rates with coinfections, even when a pathogen dose is lower.
The scientists also remove the fish from the equation altogether and are beginning research on how pathogens change their behavior simply by being near one another. Through proteomics, scientists study which proteins bacteria produce, which proteins are secreted and whether virulence-related proteins change when certain bacteria are together.
This is largely uncharted territory for researchers, but they hope to learn if bacteria compete for resources, signal to each other, “hold the door open” for secondary infections or create proteins that leave the host fish more vulnerable. This approach shifts the focus from how a pathogen affects a fish to how the pathogens affect each other.
The Auburn-USDA collaboration is uniquely positioned to address this type of research. Located nearly side by side, the university and federal research unit combine complementary expertise in immunology, genomics, bacteriology and virology. Both also have close ties with the aquaculture industry in Alabama.
“We are very blessed to have the USDA Aquatic Animal Health Research Unit here at Auburn next to us,” Bruce said.
The work is supported through congressional appropriations. Now entering its fifth year, the team has expended more than $3 million on aquaculture research benefiting the Southeast and beyond.
The direction of the federally funded coinfection research is shaped by local input from the aquaculture industry. The team has focused extensively on Flavobacterium covae, one of four Columnaris-causing bacteria and is one of the primary killers of channel catfish. Flavobacterium covae costs the Alabama catfish industry nearly $30 million annually. (LaFrentz discovered Flavobacterium covae and named it in honor of his colleague and Auburn fisheries professor Covadonga “Cova” Arias.)
Beyond advancing basic scientific understanding, the team’s goal is to produce results that can be immediately useful to industry. That doesn’t always mean a new vaccine or treatment. Oftentimes, it’s simply better guidance about how to manage multiple diseases when they appear.
“It might not be the product itself,” LaFrentz said. “It may be the cognizance to change management strategies.”
As the project enters its fifth year, the researchers are expanding their focus to examine how vaccines, antibiotics, probiotics and feed-based interventions perform in the presence of coinfections. Using combinations of vaccines and probiotics with antibiotics is important, as there are only three FDA-approved antibiotics for aquaculture, Bruce said. Antibiotic resistance is always a concern, and much of the work seeks to vary and make more strategic use of existing antibiotics.
The team distributes its findings directly to producers through newsletters, Alabama Cooperative Extension field days and the annual Catfish Conference.
