Fighting antimicrobial resistance in aquaculture: new findings on PACAP antibacterial activity support host defense peptides as alternatives in aquaculture
Mario Pablo Estrada, Yamila Carpio
Agricultural Biotechnology Direction, Center for Genetic Engineering and Biotechnology (CIGB)
The United Nations 2030 Agenda for Sustainable Development recognizes aquaculture as a vital contributor to both livelihoods and food security, with its production anticipated to surge in the coming years. Climate change and inadequate management practices have heightened the vulnerability of farmed species to pathogens. Antibiotics have become the primary choice for controlling bacterial diseases in aquaculture. It is estimated that as much as 80% of the antibiotics administered to fish ultimately end up in the water, where they spread rapidly through aquatic systems. Several alternatives are currently being developed to reduce the reliance on antibiotics for controlling pathogens in aquaculture. Among these, the following are particularly noteworthy: Bacteriophages, production of specific pathogens-free (SPF) larvae of fish and shellfish, vaccines, use of prebiotics and probiotics and antimicrobial peptides (AMP).
The objectives of our research are the characterization of neuropeptide PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) as a novel antimicrobial peptide in teleost fish. PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) is a multifunctional neuropeptide (38 amino acids) belonging to the vasoactive intestinal peptide (VIP)/secretin/glucagon superfamily. It acts throughout the body by elevating intracellular cyclic AMP (cAMP) levels via interaction with specific G protein-coupled receptors, playing critical roles in neuroprotection, endocrine regulation, stress responses, and homeostasis. Recent studies showed that PACAP have definitively classified as a broad-spectrum AMP. It exhibits direct antimicrobial activity against bacteria, fungi and viruses, while also possessing potent immunomodulatory and cytoprotective properties.
To fulfill these objectives we developed several methodologies for in vitro and in vivo experiments with fish cells, cell lines or different fish species. Different administration routes were assayed in vivo such injection, nasal administration or oral. The results showed that PACAP- supplemented diets, especially with amidated PACAP, reduced mortality and initiated the immunological pathways to resolve bacterial infections. Future work should assess different dosages and feeding regimes of amidated PACAP to determine optimal dosing and strategic therapy to maximize impacts on infection and survival in teleost.
