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

Streptococcus suis is one of the most important zoonotic pathogens threatening the lives of pigs and humans. Increasingly severe antimicrobial resistance in S. suis is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment of S. suis infections. The current study investigated aurisin A, an aristolane dimer sesquiterpene isolated from the luminescent mushroom Neonothopanus nambi Speg. (Marasmiaceae), against S. suis. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of aurisin A against S. suis 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 S. suis, 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 S. suis 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 S. suis in lung epithelial cells in a concentration-dependent manner. Additionally, aurisin A significantly reduced the hemolytic effect of S. suis 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 S. suis 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.