Linalool combats Saprolegnia parasitica infections through direct killing of microbes and modulation of host immune system

<i>Saprolegnia parasitica</i> is one of the most virulent oomycete species in freshwater aquatic environments, causing severe saprolegniasis and leading to significant economic losses in the aquaculture industry. Thus far, the prevention and control of saprolegniasis face a shortage of medications. Linalool, a natural antibiotic alternative found in various essential oils, exhibits promising antimicrobial activity against a wide range of pathogens. In this study, the specific role of linalool in protecting <i>S. parasitica</i> infection at both in vitro and in vivo levels was investigated. Linalool showed multifaceted anti-oomycetes potential by both of antimicrobial efficacy and immunomodulatory efficacy. For in vitro test, linalool exhibited strong anti-oomycetes activity and mode of action included: (1) Linalool disrupted the cell membrane of the mycelium, causing the intracellular components leak out; (2) Linalool prohibited ribosome function, thereby inhibiting protein synthesis and ultimately affecting mycelium growth. Surprisingly, meanwhile we found the potential immune protective mechanism of linalool in the in vivo test: (1) Linalool enhanced the complement and coagulation system which in turn activated host immune defense and lysate <i>S. parasitica</i> cells; (2) Linalool promoted wound healing, tissue repair, and phagocytosis to cope with <i>S. parasitica</i> infection; (3) Linalool positively modulated the immune response by increasing the abundance of beneficial Actinobacteriota; (4) Linalool stimulated the production of inflammatory cytokines and chemokines to lyse <i>S. parasitica</i> cells. In all, our findings showed that linalool possessed multifaceted anti-oomycetes potential which would be a promising natural antibiotic alternative to cope with <i>S. parasitica</i> infection in the aquaculture industry.