Alternative Strategies to Combat Antibiotic-Based Treatment in Aquaculture

*By Kunal Samadhan Tayde, Nayan Chouhan, Manish Kumar and Bhavesh Choudhary

Antimicrobials have significantly enhanced the health and well-being of animals; nevertheless, their effectiveness has been undermined by the evolution of antimicrobial resistance (AMR) in reaction to their use. The emergence of AMR in farmed fish is a significant concern in aquaculture. Alternatives to antimicrobial treatments include effective husbandry, appropriate feed formulation, vaccinations, biological control agents, and immunostimulants.

Introduction

The discovery of antibiotics in the early 20th century alleviated several life-threatening disorders (Kalia et al., 2007). Nearly a century later, the excessive and indiscriminate use of antibiotics has resulted in the formation of multiple drug-resistant (MDR) bacterial strains (Ciofu et al., 1994).

The escalation of aquaculture to satisfy the growing demand for fish has resulted in the endorsement of circumstances conducive to the use of various chemicals and pharmaceuticals to combat microbial infections. Antimicrobials have significantly enhanced the health and well-being of animals; nevertheless, their effectiveness has been undermined by the evolution of antimicrobial resistance (AMR) in reaction to their use.

The emergence of AMR in farmed fish is a significant concern in aquaculture. AMR is increasingly acknowledged as a significant worldwide public health issue, exacerbated by the indiscriminate use of antimicrobial drugs in both human and animal health, as well as their prevalence in the environment.

The increased incidence of bacterial diseases in fish necessitates the frequent use of antibiotics, resulting in their persistence in aquatic ecosystems and thus fostering the emergence of antibiotic-resistant bacteria. AMR in aquaculture may be transmitted to clinically significant strains in the natural environment via horizontal gene transfer, conjugation, transmission, transduction therefore impacting the whole ecosystem.

Microbial resistance in aquaculture renders disease treatments ineffective, exacerbates disease severity, diminishes output, and results in economic losses. Furthermore, over fifty percent of the antimicrobials administered to animals and fish are excreted as waste, so polluting soil, water, and the environment. This also facilitates the evolution and dissemination of resistance by exerting selection pressure on environmental microbes.

Many cultivated fish species, including ornamental varieties, harbour many infections that demonstrate numerous antibiotic resistances. Furthermore, antimicrobial use may result in the presence of antimicrobial residues in consumable animal or fish products, posing a potential public health concern.

The overuse of antibiotics in aquaculture has generated significant apprehension about antimicrobial resistance, environmental deterioration, and the disturbance of microbial ecosystems. To promote sustainable aquaculture and alleviate the detrimental impacts of antibiotic overuse, many alternative solutions have been investigated. This article emphasises potential alternatives to antibiotic therapy in aquaculture.

Although chemical-based medications are effective and beneficial, their usage results in environmental degradation and presents health risks to people upon consumption (Hoque et al., 2016). Alternatives to antimicrobial treatments include effective husbandry, appropriate feed formulation, vaccinations, biological control agents, and immunostimulants (Figure 1).

Prebiotics and Probiotics

Prebiotics are a non-digestible food ingredient which when consumed shows beneficial effect on gut microbes. It includes fructooligosaccharides and inulin, that enhance the proliferation of advantageous gut microbiota, hence indirectly augmenting disease resistance.

Numerous prebiotics are often used in aquaculture, hence enhancing the immune systems of fish and other aquatic organisms. Prebiotics are sourced from several origins, including mannan oligosaccharides, fructo-oligosaccharides and galacto-oligosaccharides.

Probiotics are live advantageous bacteria that promote fish health when provided in sufficient amounts by battling with infections, enhancing digestion, and strengthening immune. It aids in maintaining a balanced microbial ecosystem, especially inside the digestive tract, by fostering a healthy equilibrium of gut bacteria, enhancing digestion, and influencing immune system regulation.

Probiotics often used in aquaculture include organisms from the genera Lactobacillus, Bacillus and Pseudomonas. The incorporation of prebiotics and probiotics into fish diets enhances and co-modulates the immune system.

Plant-Derived Compounds and Essential Oils

Plant-derived bioactive chemicals often known as phytobiotics provide antibacterial and immunostimulatory capabilities. These compounds are attractive supplements and alternatives owing to their efficacy, tolerability, environmental sustainability and reduced medication resistance.

The use of polyphenols, polyphenol-rich flora and plant-derived phenolic compounds to enhance aquatic animal health and wellbeing may represent viable ways for advancing pathogenic microbial mitigation strategy and ensuring the sustainability of the aquaculture sector.Numerous plants possess aesthetic appeal due to their diverse bioactive compounds, namely phytochemicals and polyphenols.

Phytocompounds are bioactive substances present in several plant species and possess significant potential. Extracts from garlic (Allium sativum), neem (Azadirachta indica) and turmeric (Curcuma longa), etc. have shown effectiveness against fish infections without promoting AMR.

The incorporation of aquatic plants in aquaculture may be the optimal solution to address these issues and advance sustainable aquaculture output (Hossain et al., 2024).Essential oils extracted from thyme, oregano, cinnamon and eucalyptus have antibacterial activities that suppress fish infections. according to several studies the integration of these compounds directly into feed formulations, bath and dip treatments helps mitigate disease without the danger of development of resistance.

Bacteriophage Therapy

Bacteriophages were identified and designated by Felix d’Herelle in 1917 (d’Herelle, 1961). Bacteriophages are the natural adversaries of bacteria and are efficacious in combating bacterial infections.

In aquaculture, phage therapy is gaining recognition as a viable alternative to antibiotics for addressing bacterial infections. Bacteriophages are viruses that exclusively infect and destroy bacterial pathogens.This method is highly targeted, ecologically sustainable, and does not disturb advantageous microbial populations.

The three predominant families of bacteriophages in aquatic ecosystems are Myoviridae, Siphoviridae and Podoviridae. In contrast to antibiotics, phages have a reduced issue of bacterial resistance. Bacteriophages provide a unique advantage over antibiotics by continuously multiplying at the infection site as long as the host bacteria are there (Choudhury et al., 2017).

Phage treatment would be especially beneficial during the first phases of fish development, such as eyed-eggs and fry, which possess an underdeveloped immune system and are thus unable to use vaccinations (Bhat and Altinok, 2023).

Phage treatment has shown efficacy against Aeromonas hydrophila, Vibrio spp, and several prevalent aquaculture diseases.Since 2011, phages have been regarded as a therapeutic agent in the United States (Fauconnier, 2019) or a pharmaceutical product in the European Union.

A chemical or mixture of substances designed to cure, prevent, or diagnose a disease, or to restore, correct, or change physiological functioning by pharmacological, immunological, or metabolic actions, as defined by the European Medicines Agency (EMA).

Immunostimulants

An immunostimulant is a naturally occurring chemical that enhances the immune system by augmenting the host’s resistance to diseases often induced by infections (Bricknell and Dalmo, 2005).

Inactivated natural microorganisms or microbial derivatives, including beta-glucans, lipopolysaccharides, lactoferrin, nucleotides, chitin, fucoidan, peptidoglycans, and certain polysaccharides, might elicit immune system activation.Immunostimulants that may enhance and elicit a robust defensive response in the host include polysaccharides, hormones, vitamins, various bacterial components, physiologically active substances, traditional Chinese medicines, and synthetic pharmaceuticals (Kasahara amp; Sutoh, 2014; Buchmann, 2014; Shrestha et al., 2015).

These chemicals enhance the capacity of fish to combat illnesses independently of antibiotics. Immunostimulants are essential for provoking immunological responses that may provide comprehensive protection against certain infections (Wang et al., 2017). The use of natural immunostimulants in aquafeeds to enhance immune response shows promise in augmenting disease resistance (Traifalgar et al., 2013).

Vaccination

Vaccination serves as a compelling strategy to prevent the onset of infections and diseases in people and animals, diminishing antibiotic use and hence hindering the formation and dissemination of resistance microorganisms.

The mechanism through which vaccines diminish pathogens and AMR circulation markedly differs from that of antibiotics, leading to minimal selective pressure on microorganisms; consequently, the likelihood of resistant pathogen emergence is significantly lower compared to antibiotics (Murugaiyan et al., 2022).

Vaccination offers enduring protection against bacterial and viral diseases. Vaccines provide a direct and indirect function in combating AMR. Vaccines directly impact resistant pathogens by decreasing infection rates and indirectly by diminishing the transmission of AMR-resistant strains to non-resistant species.

A decreased prevalence of infections is associated with a lower prescription of antibiotics and a lowered occurrence of secondary infections and superinfections that would otherwise need extensive antibiotic use. Vaccines have been successfully produced for Aeromonas, Edwardsiella, and Streptococcus infections in aquaculture species.

Progress in oral and immersion vaccinations is enhancing the feasibility of immunisation for extensive fish farming. Vaccine resistance has been recorded for many significant diseases, including the hepatitis B virus (Hoan et al., 2021) and Bordetella pertussis (Octavia et al., 2014).

Quorum Sensing (QS) Inhibitors

QS is a bacterial cell-cell communication system that regulates several processes, including biofilm formation, virulence gene expression and stress adaption. The process encompasses the synthesis, secretion and identification of extracellular signalling molecules known as autoinducers (Gupta and Kumar, 2022).

Bacteria function as unicellular creatures at low cell densities; but they may alter their behaviour to a “multicellular” form upon detecting that their population density has reached a critical threshold.

At this juncture, they convey information by diminutive signalling molecules, which facilitate the expression of genes associated with various phenotypes, including those governing their virulent behaviour.

Opportunistic pathogens such as Pseudomonas aeruginosa tend to remain “dormant” and postpone their virulent phenotype until their population reaches a level sufficient to surpass the host’s defence systems.The QS process can be impeded by various mechanisms:

(i) diminishing the activity of AHL cognate receptor proteins or AHL synthases,

(ii) obstructing the synthesis of QS signal molecules,

(iii) degrading AHL, and

(iv) mimicking signal molecules, primarily through the use of synthetic compounds as analogues.

Among several options, the enzymatic degradation of quorum sensing signal molecules (AHLs) has been the most recognised and used (Kalia and Purohit, 2011).

Metal-Based Antibacterial Agents

Historically, metal ions have often been used for antibacterial applications (Alexander, 2009). Metals may be complexed with a biomolecule, complexed with an antibiotic, or used with an antibiotic for antibacterial applications.

The use of metal-based antibiotics has the benefit of varied mechanisms of action in contrast to traditional organic antibiotics (Simpson et al., 2019).Furthermore, the incorporation of metals into organic antibiotics allows innovative and supplementary mechanisms of action in contrast to the organic drug alone (Gasser, 2015).

Consequently, the use of these metalbased complexes, either alone or in conjunction with antibiotics, shows potential as an efficacious therapy for resistant bacterial infections via innovative and supplementary mechanisms of action (Table 2).

Conclusion

The growing awareness of antibiotic resistance has accelerated the search for alternative strategies in aquaculture. Probiotics, phytobiotics, bacteriophage therapy, immunostimulants, vaccination, and essential oils are emerging as effective solutions.

A combination of these approaches, tailored to specific aquaculture systems, can significantly reduce dependence on antibiotics while ensuring sustainable fish production.

Several methods discussed here are still in research phase, while some are tested in real aquaculture farm settings. Therefore, it is essential to advance several techniques that may be integrated or used in succession to optimise the likelihood of effectively safeguarding the animals and to avert the development of resistance.

References and sources consulted by the author on the elaboration of this article are available under previous request to our editorial staff.

Kunal Samadhan Tayde, Nayan Chouhan, Manish Kumar and Bhavesh Choudhary

College of Fisheries, Central Agricultural University, Lembucherra, Tripura, 799210

Email: nayan101chouhan@gmail.com