Climate Friendly Methods for Treating Fish Bacterial Diseases in Aquaculture that are Safe for the Environment in the Black Sea Region
Introduction
In food safety applications, phages have already obtained approval from the US FDA and are regularly used in meat or agricultural products to prevent the spread of bacteria responsible for food spoilage as well as infection from food borne pathogens. Phages are being used more frequently and will soon be produced on a wide scale due to their extremely specialized activity [1].
It is essential that agriculture be able to sustainably feed a growing global population. Since the introduction of crop cultivation and animal husbandry techniques, bacterial illnesses of plants and animals have steadily decreased production.
Numerous antibiotics have been employed to reduce these losses. However, the growth of bacteria that are resistant to antibiotics (AMR) and consumer demands for products devoid of antibiotics offer issues that endanger sustainable agriculture. Alternatives to antibiotics for controlling bacterial populations include bacteriophages (phages).
Their unique properties make them highly promising but challenging antimicrobials. The use of phages in agriculture also presents a number of unique challenges [2].
Phage therapy may represent a viable alternative to antibiotics to inactivate fish pathogenic bacteria. Its use, however, requires the awareness of novel kinetics phenomena not applied to conventional drug treatments. The main objective of this work was to isolate bacteriophages with potential to inactivate fish pathogenic bacteria, without major effects on the structure of natural bacterial communities of aquaculture waters [3].
To reduce the risk of development and spreading of antibiotic resistant bacteria, other more environmentally friendly methods to control fish disease in aquaculture must be developed. In line with this idea, the use of phage therapy in aquaculture seems to be very promising, as bacterial diseases are a major problem in the expanding aquaculture industry [4,5,6].
Bacteriophages, often known as phages, are extremely prevalent bacterial viruses in nature that are thought to be crucial in managing bacterial populations in natural systems. They are even multidrug resistant. It appears especially promising to employ phages to control infections in aquatic environments, such as fish illnesses. The therapeutic phages can maintain constant and close physiological contact with the pathogens in a natural setting since the host fish organisms exist in watery environments. In fact, some research has shown that phage therapy has the potential to be used to control disease in aquaculture systems. [7,8,9,10].
Fish infection by pathogenic bacteria is a growing issue for the global expansion of aquaculture. Numerous chemotherapies, such as the use of antibiotics, have facilitated the development of a quick and efficient means of treating or preventing bacterial infections. The need for novel strategies to manage fish pathogenic bacteria is brought on by the growing issue of antibiotic resistance in common pathogenic bacteria and the worry that antibiotics are spreading across the ecosystem. Phage therapy therefore represents a potentially effective substitute for antibiotics and other antimicrobial substances to inactivate native and foreign harmful bacteria in fish farming facilities [3].
The success of phage therapy in aquaculture depends mainly on the phages selected to inactivate the fish pathogenic bacteria [11]. The selected phages must remain viable in marine waters, infecting pathogenic bacteria but not altering significantly the non-pathogenic bacteria that have an important ecological role. Unlike antibiotics, phages are self-replicating as well as self-limiting and, consequently, they replicate exponentially as bacteria replicate and decline when bacterial numbers decrease [12,13,14].
The bacterial community structure of the total and pathogenic bacterial communities fluctuated seasonally in this aquaculture system, with the warm season demonstrating a higher complexity, according to earlier studies. The authors came to the following conclusions: (1) The seasonal variation of the bacterial communities suggest the need for careful water monitoring throughout the year in order to choose suitable phages to inactivate fish pathogenic bacteria; and (2) the spring season appears to be the crucial time period when phage therapy should be used. As a result, the effect of the phages on the makeup of the bacterial population can also change with the season. However, the investigation of the phages' effects on the bacterial population should be carried out in the summer, which is the crucial time frame for using phage treatment [15].
Additionally, a number of phage cocktail products aim to infect these bacteria. To prevent and control bacterial illnesses, the majority of veterinary phage products are primarily in the form of food additives in animal feed or drinking water.
Phage cocktails can broaden the spectrum of potential hosts and avoid focusing on a particular pathogen. [16].Additionally, prior to receiving customized therapy with phages, quick identification of bacterial pathogens is a tedious and time-consuming process. [17].
In general, a phage cocktail can be utilized not only for the prevention and treatment of various bacterial infections but, also, for the control of phage-resistant bacteria that may occur during mono-phage application [18]. The phage resistance mechanisms of bacteria have been widely studied, including the prevention of phage adsorption, blocking of phage receptors, production of extracellular matrix, and production of competitive inhibitors [19]. A competition for the same receptor in each phage may result from the usage of cocktail phages. Phage mixtures do not show infectivity against the mono-phage-resistant strain if the infection mechanisms used by the many phages are the same. In order to produce phage cocktails, it is advised that the infectious mechanism of each phage be taken into account.
The consequences of this active bacterial lysis propagate upwards in the trophic chain and alter carbon transfer from atmosphere to sediments and are hypothesized to eventually have effects on the
climate as well [20].
These results prove that phages’ high numbers and key role in the marine trophic chain grant them a global impact. As the current understanding of microbial communities is limited, disrupting them with antimicrobials like phages could yield unforeseen global consequences. This should be kept in mind during the design of a product impacting these communities [21].The main known impacts phage therapy can have on the environment are genetic transfer through transduction, development of bacterial resistance and disruption of the microbiome. Assessing the impact of phage therapy on the environment is especially important in our case since the aquatic environment acts as a vector for phages, allowing a quick dissemination [22]. This is due to their ability to reproduce in situ and to the existence of an effectiveness threshold: if the phages are introduced in a small quantity their concentration might be below the critical point where they can effectively kill bacteria and the therapy will therefore fail. On the other hand, if they are able to reproduce freely, phages are likely to spread and persist in the environment [23]. This persistence is not ideal since it potentially provides the treatment with an impact outside of the aquaculture system. Although we lack long term experience on environmental phage therapy, the majority of published work failed to highlight any major risk associated to phage-mediated microbial community disruption which is probably due to their host specificity. Despite their apparent harmlessness, it is important to test each and every phage’s impact on the treated microbial community before using it at industrial scale.
