We at fishPHARM believe sustainable and efficient aquaculture is one of the best ways of providing a growing global population with the food it needs to thrive. The overuse of antibiotics on today’s fish farms is detrimental to both the consumer and the aquaculture industry. Outbreaks of bacterial coldwater disease (BCWD) and lack of efficient preventative monitoring systems are real issues that affect the productivity of fish farmers today. We make it our mission to produce antibiotic-free treatments for BCWD, design and manufacture effective and safe drug delivery methods for aquacultured fish, and design and manufacture farm monitoring systems for the purpose of disease prevention and general fish well-being. With these initiatives, fishPHARM will help aquaculture around the globe attain a more sustainable position for food production.
Cornell University is situated in the heart of the Finger Lakes region of Upstate New York where a diverse array of salmonid fish call home. Unfortunately, the region has been impacted by a series of bacterial coldwater disease (BCWD) outbreaks, severely reducing the number of fish available for recreational fishing and local aquaculture. BCWD is a potentially lethal bacterial infection of salmonid fish species caused by the pathogen Flavobacterium psychrophilum. Fish suffering from BCWD develop skin lesions that effectively renders the fish inedible and unviable. The disease is not only found in Upstate New York, but also has been cited in other fish farms and hatcheries where fish are raised in close quarters. In fact, other American fish farms have reported instances in which over 30-45% of trout raised have been lost due to BCWD . The grave economic and agricultural consequences of BCWD are unresolved by current means of treatment consisting of antibiotics. This year, Cornell iGEM has developed fishPHARM: a comprehensive prevention and treatment plan that uses the tools of synthetic biology to combat BCWD.
Since the etiology of BCWD is characterized by intra-organismal microbial proliferation, our treatment protocol seeks to reduce microbial loads within the infected fish through the use of a peptide called Entericidin B. Recent studies have shown the peptide to be toxic to the growth of Flavobacterium psychrophilum, thereby providing a potential treatment to BCWD. Hundreds of bacterial entericidin phenotypes exist naturally. This year, Cornell iGEM has engineered 20 strains of Escherichia coli for the regulated production of such peptides to test their efficacy against the growth of Flavobacterium psychrophilum. In doing so, we plan to develop the most effective probiotic treatment for BCWD and advance the study of therapeutic probiotic treatments in combatting similar diseases.
In addition, the team engineered a novel fish drug delivery system to safely administer our probiotic treatment without environmental harm. We have developed a working prototype of a fish tag that can safely latch onto the skin of a fish and demonstrate the secure and time-effective release of our peptide to treat BCWD in an infected fish. Our fish tag aligns with current practices of fish tagging in the aquaculture industry today, and has immediate potential to be implemented on both a local and global scale. We have shared the device with local hatcheries and fish farms to both garner feedback to improve prototype designs as well as help local farmers combat coldwater disease.
Success of this putative microbial control system holds important ramifications for human and animal health, as similar treatment methods could be devised for other bacterial infections. Prevention of BCWD will help provide a more secure, sustainable future in the fish industry and beyond to aid growing population necessary to sustain the continued increase of the human population.
The Disease: Bacterial coldwater disease (BCWD) is a bacterial infection among fish caused by Flavobacterium psychrophilum, a Gram-negative bacillus. The name of the disease is derived from the fact that infection typically occurs at temperatures below 13 degrees Celsius . The rapid spread of this waterborne disease occurs through horizontal transmission of bacteria from one fish to another, and is exacerbated when fish are contained in dense populations such as those commonly found on fish farms . Symptoms of BCWD include external fish skin lesions and necrosis of the fins, both of which render fish commercially inviable .
Local BCWD Outbreaks: Cornell University is situated in the Finger Lakes region as well as a part of the Great Lakes region. Unfortunately, the region has recently been hard hit by the effects of BCWD. For example, in 2010, Wolf Lake State Fish Hatchery, a Ohio facility associated with Lake Erie, reported an outbreak of BCWD among its stock of steelhead. Mortality rates among its 285,000-fish population rapidly reached 100 individual salmonids per day. By the time antibiotics were administered, mortalities had peaked at 371 fish a day . Rampant BCWD infections in our local area has inspired us to create fishPHARM to help prevent local infections from spreading.
Aquaculture and Fish Farming: Outbreaks of BCWD are very common, observed globally, and can result in harsh economic effects on commercial salmonid producers . Wild salmonid populations are also susceptible and wild fish can easily contract the disease via contact with domestic populations . At principal risk are farms in the United States that grow salmonids in cramped conditions. Aquacultural production of salmonids is one of the the fastest growing and largest food markets globally, producing hundreds of millions of tons of fish and representing a market worth hundreds of billions of dollars. Fish farming has been a rapid response to the growing crisis of global overfishing. In addition to ensuring that hungry populations have access to a cheap yet nutritious source of protein, aquaculture provides fishermen with a means of compensating for the shrinkage of wild fish populations. Heavily populated countries such as Norway, Chile and Japan are leading consumers of aquacultural products, and rely on farm-grown fish to help feed the masses. Epidemics among fish farms could thus have disastrous consequences. The aim of our project is not only to prevent economic harm to the fishermen, but to aid communities with economies heavily dependent on the aquaculture industry and provide food security as well.
Threat to Wildlife: BCWD is not only a threat to the commercial fish farming industry, but also a concern to the ecology of the wild salmonid fish population. When these fish farms are located in larger bodies of water, the pathogen F. psychrophilum can escape natural or man-made boundaries to infect wild fish populations . Compounding to this problem is the fact that juvenile fish, which are more susceptible to infection, are commonly found in estuaries and bays where the fish farms are usually placed. Since salmon are a crucial source of nutrition for a plethora of secondary and tertiary consumers (bears, otters and ospreys, for instance), mass die-offs among the fish could devastate local ecosystems . Containing F. psychrophilum is thus crucial to both the economic and ecological well-being of the earth's natural habitat.
Current Solutions: The current treatment protocols for BCWD involve chemotherapeutic agents. Broad-spectrum antibiotics such as oxytetracycline are currently being used by fish farms to treat BCWD , but these antibiotics remain in the food we consume, leach into the ocean or soil surrounding farms, and give bacteria the opportunity to develop resistance. Antibiotic resistance reduces the effectiveness of the administered antibiotic in successive generations, thereby worsening the effects of BCWD over time. This prompts the need for a treatment for BCWD that is less prone to resistance than antibiotics.
Ryce, E., & Zale, A. (2004). Bacterial Coldwater Disease in Westslope Cutthroat Trout: Hatchery Epidemiology and Control. Retrieved from the Wild Fish Habitat Initiative Website: http://wildfish.montana.edu/docs/BCWD_FinalReportJune2004.pdf
Schubiger, C., Orfe, L., Sudheesh, P., Cain, K., Shah, D., & Call, D. (2014). Entericidin Is Required for a Probiotic Treatment (Enterobacter sp. Strain C6-6) To Protect Trout from Cold-Water Disease Challenge.Applied and Environmental Microbiology Appl. Environ. Microbiol.,81(2), 658-665.
 Starliper, Clifford. "Bacterial Coldwater Disease of Fishes Caused by Flavobacterium Psychrophilum." Bacterial Coldwater Disease of Fishes Caused by Flavobacterium Psychrophilum. Journal of Advanced Research, n.d. Web. 14 Sept. 2015.
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