Paeoniflorin reduce <i>luxS</i>/AI-2 system-controlled biofilm formation and virulence in <i>Streptococcus suis</i>

Abstract

<i>Streptococcus suis</i> (<i>S. suis</i>), more specifically serotype 2, is a bacterial pathogen that threatens the lives of pigs and humans. Like many other pathogens, <i>S. suis</i> exhibits quorum sensing (QS) system-controlled virulence factors, such as biofilm formation that complicates treatment. Therefore, impairing the QS involving LuxS/AI-2 cycle in <i>S. suis</i>, may be a promising alternative strategy for overcoming <i>S. suis</i> infections. In this study, we investigated paeoniflorin (PF), a monoterpenoid glycoside compound extracted from peony, as an inhibitor of <i>S. suis</i> LuxS/AI-2 system. At a sub-minimal inhibitory concentration (MIC) (1/16 MIC; 25 μg/ml), PF significantly reduced biofilm formation by <i>S. suis</i> through inhibition of extracellular polysaccharide (EPS) production, without affecting bacterial growth. Moreover, evidence was brought that PF reduces AI-2 activity in <i>S. suis</i> biofilm. Molecular docking indicated that LuxS may be the target of PF. Monitoring LuxS enzymatic activity confirmed that PF had a partial inhibitory effect. Finally, we showed that the use of PF in a mouse model can relieve <i>S. suis</i> infections. This study highlighted the anti-biofilm potential of PF against <i>S. suis</i>, and brought evidence that it may as an inhibitor of the LuxS/AI-2 system to prevent <i>S. suis</i> biofilm-related infections. PF can thus be used as a new type of natural biofilm inhibitor for clinical application.