Growing Trend of Fighting Infections in Aquaculture Environment—Opportunities and Challenges of Phage Therapy

Abstract

Phage therapy, a promising alternative to antimicrobial treatment of bacterial diseases, is getting more and more popular, especially due to the rising awareness of antibiotic resistance and restrictions in antibiotics’ use. During recent years, we observed a growing trend of bacteriophages’ application in aquaculture, which in each year reports high losses due to bacterial diseases. This review provides an update of the status of bacteriophage therapy for the treatment and prevention of infections in the aquatic environment. As it is still mostly in the scientific stage, there are a few constraints that may prevent effective therapy. Therefore, specific characteristics of bacteriophages, that can act in favor or against their successful use in treatment, were described. We underlined aspects that need to be considered: specificity of phages, bacterial resistance, safety, immune response of the host organism, formulation, administration and stability of phage preparations as well as bacteriophages’ influence on the environment. The biggest challenge to overcome is finding the right balance between the desired and problematic characteristics of bacteriophages. Finally, regulatory approval challenges may be encountered by bacteriophage manufacturers. Even though there are still some technical constraints connected with the global use of bacteriophage therapy, it was concluded that it can be successfully applied in aquaculture.

Molecular Characterization of Ahp2, a Lytic Bacteriophage of Aeromonas hydrophila

“…In fact, phage preparations have already been used clinically and in agriculture for treating bacterial infections [ 55 , 56 , 57 ]. Furthermore, many tests have been conducted experimentally to evaluate the efficacy of phage therapy on Aeromonas infections that showed promising results [ 58 , 59 , 60 ]. As bacterial resistance to phage infection is a major issue for phage therapy, isolating new phage strains is crucial.…”

Phage-Mediated Control of Flavobacterium psychrophilum in Aquaculture: In vivo Experiments to Compare Delivery Methods

“…Based on previous challenge experiments (data not published and Christiansen, 2014 ), where we detected an early onset of mortality in fish exposed to crude lysates of phages, we decided to PEG purify phage solutions in order to decrease the concentration of compounds that could be toxic for the fish. Gram negative bacteria produce endotoxins which might induce allergic reactions ( Kowalska et al, 2020 ). For the fish experiments, 1 L of bacterial cultures (OD 600 nm = 0.2) were separately infected with the phages FPSV-D22 and FpV4 at MOI = 1 ( F. psychrophilum FPS-S6 and 950106-1/1, respectively) and incubated for ∼3 days.…”

“…focusing, e.g., on the isolation and characterization of virulent phages (Kalatzis et al, 2016;Kazimierczak et al, 2019), cocktail formulations (Mateus et al, 2014;Duarte et al, 2018), dose and route of phage administration (Laanto et al, 2015;Almeida et al, 2019). However, despite the many benefits of phage therapy, various challenges have been faced such as the development of phage resistant bacteria, the inefficient delivery of phages in high dosages at the infection site, and the phage clearance activity from the organism mediated by the immune cells [reviewed in Culot et al (2019); Kowalska et al (2020)].…”

“…Flavobacterium psychrophilum ( Borg , 1948 ; Bernardet et al, 1996 ) is the etiological agent of Rainbow Trout Fry Syndrome (RTFS, fry stage) ( Lorenzen et al, 1991 ) and of Bacterial Coldwater Disease (BCWD, juvenile and adult fish) ( Borg, 1960 ). Rainbow trout ( Oncorhynchus mykiss , Walbaum) and coho salmon ( Oncorhynchus kisutch ) are the most susceptible salmonid species to this bacterium ( Nematollahi et al, 2003 ).…”

Interactions between Rainbow Trout Eyed Eggs and Flavobacterium spp. Using a Bath Challenge Model: Preliminary Evaluation of Bacteriophages as Pathogen Control Agents

“…The utilization of virulent bacteriophages (also called phages) [ 20 ] to reduce mortality and prevent the spread of bacterial populations among fish and crustaceans at different stages has gained increased attention (reviewed by [ 21 , 22 ]). Phage therapy is considered a potential alternative to antibiotics, aiming to reduce the issues related to the use of antibiotics, and as a preventive measure against the spread of bacterial infections (reviewed by [ 23 ]).…”