Endolysin for the treatment of Streptococcus iniae in hybrid striped bass

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By Milthon Lujan

Hybrid striped bass. (Photo by Matt McEntire, ARS)
Hybrid striped bass. (Photo by Matt McEntire, ARS).

As aquaculture trends shift towards recirculation systems, the risk of horizontal transmission of Streptococcus iniae among fish intensifies. Current vaccination strategies provide only short-term protection, leading to widespread antibiotic use, particularly florfenicol. However, this practice raises environmental concerns and contributes to the growing antibiotic resistance issue. In light of these challenges, alternative strategies are urgently needed.

Scientists from the United States Department of Agriculture’s Agricultural Research Service (ARS) have developed a green antibiotic alternative to treat the deadly pathogen Streptococcus iniae in hybrid striped bass, the fourth most cultivated fish in the United States, according to a recent study.

Streptococcus Iniae


S. iniae is the causative agent of streptococcosis, a prevalent disease in aquaculture causing a global economic loss of $150 million annually. Disease outbreaks can lead to the bankruptcy of fish farms and put aquaculturists at risk of contracting the disease while handling infected fish.

The repercussions of outbreaks extend beyond financial losses, with documented cases leading to the bankruptcy of two large hybrid striped bass (HSB) farms in the U.S. The increase in human infections, attributed to handling infected fish, underscores the urgency of finding effective solutions.

Current vaccines provide only short-term protection against S. iniae, and fish farmers often resort to antibiotics to treat the disease. ARS scientists aimed to develop a natural treatment for antimicrobial resistance, a process where germs such as bacteria and fungi develop the ability to fight drugs designed to kill them, is a major concern for aquaculturists when treating bacterial diseases.

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Endolysin Therapy: A Novel Approach

Unlike traditional antibiotics, endolysins are genus-specific and target the bacterial pathogen while preserving beneficial flora. The therapeutic potential of endolysins has been widely investigated, and ongoing human clinical trials demonstrate their promise.


The study explored the potential of endolysin therapy, derived from bacteriophages, as an alternative to traditional antibiotic treatments. Endolysins are hydrolytic enzymes that target the bacterial peptidoglycan cell walls, offering a promising avenue to combat S. iniae infections.

“Along with our collaborators, we developed a new antimicrobial protein and treatment regimen that specifically kills only Streptococcus bacteria and leaves no chemical residue in the environment,” said Michael Deshotel, a research microbiologist at the Harry K. Dupree Stuttgart National Aquaculture Research Center. “According to the results of our study, this protein effectively cures S. iniae infections in hybrid striped bass.”

The study focused on evaluating the efficacy of three synthetic endolysins (PlyGBS 90–1, PlyGBS 90–8, and ClyX-2) compared to the antibiotic carbenicillin in treating hybrid striped bass (HSB) infected with S. iniae.

Notable Bacteriolytic Potency of ClyX-2

Results revealed that ClyX-2 exhibited remarkable bacteriolytic potency, demonstrating lytic activity at concentrations as low as ~15 μg/ml. This potency was approximately 8 times higher than that of PlyGBS derivatives, suggesting a superior ability to target and eliminate S. iniae.


According to Deshotel, the protein, known as ClyX-2, showed a 95 percent survival rate for fish in the treatment groups compared to the 5 percent survival rate for fish in the control groups during the study. The results showed that the protein was statistically as effective in treating S. iniae as antibiotic treatments like carbenicillin (cure rate of 85 percent).

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Promising Alternative for Aquaculture

The findings highlight ClyX-2 as a promising alternative to combat S. iniae infections in aquaculture. Not only does it exhibit potent bacteriolytic activity, but it also offers high survival rates comparable to conventional antibiotics. This breakthrough has the potential to revolutionize S. iniae management, providing a sustainable solution while minimizing the environmental impact associated with antibiotic use.


As the aquaculture industry faces challenges posed by S. iniae infections, the emergence of ClyX-2 as a potent endolysin therapy represents a significant advancement. The study findings emphasize the effectiveness of ClyX-2 in treating S. iniae-infected fish, positioning it as a promising and environmentally friendly alternative to traditional antibiotics. Further research and development in this direction could pave the way for a more resilient and environmentally respectful approach to managing bacterial infections in aquaculture.

In the future, Deshotel and researchers plan to study how to treat water to prevent diseases caused by S. iniae before they can infect fish.


The study was funded by the National Institutes of Health.

Michael B. Deshotel
United States Department of Agriculture, Agricultural Research Service
Harry K. Dupree Stuttgart National Aquaculture Research Center
2955 Hwy. 130 East, Stuttgart, AR, 72160, USA.
Email: michael.deshotel@usda.gov

Reference (open access)
Deshotel, M. B., Dave, U. M., Farmer, B., Kemboi, D., & Nelson, D. C. (2024). Bacteriophage endolysin treatment for systemic infection of Streptococcus iniae in hybrid striped bass. Fish & Shellfish Immunology, 145, 109296.