Streptococcus suis (S. suis) is a significant zoonotic pathogen. Owing to the widespread use of antibiotics in agriculture and farming, multidrug-resistant S. suis is proliferating, posing severe public health concern. The AI-2 quorum sensing (QS) system is a ubiquitous intercellular communication mechanism in both Gram-positive and Gram-negative bacteria, including S. suis, enabling it to coordinate fundamental life processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. In this study, SKQ1 demonstrated potent bacteriostatic and bactericidal activity against S. suis, with a lower propensity for resistance development. Mechanistic analyses indicate that this effect is likely achieved by compromising the integrity and functionality of the cytoplasmic membrane. Additionally, sub-inhibitory concentrations of SKQ1 significantly inhibited biofilm formation and reduced the virulence of S. suis. Untargeted metabolomics revealed that this effect may be mediated through disruption of the AI-2 QS system associated with methionine metabolism. Further investigations demonstrated that SKQ1 reduced the production of AI-2 signaling molecules, thereby diminishing biofilm formation and virulence. Owing to its antimicrobial activity and interference with the AI-2 QS system, SKQ1 exhibited robust therapeutic efficacy against diverse models of S. suis infection, including human isolates, multidrug-resistant strains, and highly virulent strains. This study offers novel insights into antibiotic strategies for managing porcine streptococcal infections and addressing the drug resistance crisis in S. suis.

To Cite This Article: Yuan S, Yi Z, Wu J, Gao S, Quan Y, Jin W, Liu B, Wang Y, Wang S, Yi L and Wang Y, 2025. Reutilization of SKQ1's antibacterial and anti-quorum sensing activities to combat Streptococcus suis infection. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.284