Antimicrobial Activity of Aurisin A Against Streptococcus suis and Its Protective Effect on Epithelial Cells

<i>Streptococcus suis</i> is one of the most important zoonotic pathogens threatening the lives of pigs and humans. Increasingly severe antimicrobial resistance in <i>S. suis</i> is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment of <i>S. suis</i> infections. The current study investigated aurisin A, an aristolane dimer sesquiterpene isolated from the luminescent mushroom <i>Neonothopanus nambi</i> Speg. (Marasmiaceae), against <i>S. suis</i>. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of aurisin A against <i>S. suis</i> strains were in the range of 1.94-62.5 μg/mL. Scanning electron microscopy showed that aurisin A induced alterations in the cellular structure of <i>S. suis</i>, including a significantly wrinkled surface, intracellular content leakage, and cell lysis. The crystal violet staining assay illustrated that aurisin A significantly inhibited biofilm formation of <i>S. suis</i> strains at sub-MICs and exhibited strong degrading activity against the preformed biofilms. Aurisin A significantly inhibited the adhesion, cell death, and cytotoxic activities of <i>S. suis</i> in lung epithelial cells in a concentration-dependent manner. Additionally, aurisin A significantly reduced the hemolytic effect of <i>S. suis</i> on defibrillated sheep blood, indicating protective activity of aurisin A against this bacteria. Taken together, these findings highlight aurisin A as a promising therapeutic candidate for the treatment of <i>S. suis</i> infections, with key roles in inhibiting biofilm formation and hemolytic activity, as well as providing protective effects to epithelial cells, including anti-adhesion, anti-cytotoxicity, and anti-cell death activities.