Modulation of Stress-Related Protein in the African Catfish (Clarias gariepinus) Using Bacillus-Based Non-Ribosomal Peptides

Probiotics, due to their multifaceted benefits to the host, are essential in medicine, agriculture, and aquaculture. The mechanisms of their action at the molecular level are complex and less explored. Both previous research and our own investigations have highlighted that incorporating probiotics into the feed of commercial fish can increase growth and influence the expression of genes related to stress and immunity. Additionally, probiotics with antioxidant properties often exert systemic effects. The aim of this work was to explore possible mechanisms of probiotic effects on stress-related proteins in African catfish C. gariepinus using molecular docking and dynamics approaches. Stress biomarker proteins such as catalase, cytochrome P450, HSP70, metallothionein 1, and superoxide dismutase were evaluated for possible interactions with bioactive non-ribosomal peptides (NRPs) from Bacillus subtilis R5, used as ligands. The study involved molecular docking and dynamics interactions between proteins and NRPs. The results of molecular docking and dynamics reveal multiple bindings between proteins and ligands, forming stable complexes, which may explain the mechanisms of action of probiotics and their particularly positive effects, such as the reduction in stress levels, which was demonstrated in the clarium catfish model in our previous work. Non-ribosomal peptides synthesized by probiotics may influence key signalling pathways underlying antioxidant and antimutagenic properties.