The Inhibitory Effect Of Morin On Streptococcus Suis Suilysin

Streptococcus suis(S.suis),an important zoonotic gram positive opportunities pathogenic bacteria,is worldwide distribution that can cause human and animal diseases,such as meningitis,encephalitis,pneumonia,arthritis,sepsis.The infection caused by S.suis seriously threaten the development of pig industry and public health.To successfully establish infection,S.suis should break epithelial barrier,evade immune system,survival and invade various organs,thereby expanding the local inflammation.All of these steps are associated with a variety of virulence factors produced by S.suis,such as capsular polysaccharide,hemolysin,muramidase released protein and cytokines.Among these virulence factors,the proe forming toxin suilysin(SLY)is one of the most well characterized virulence factor,which plays an important role in the pathogenesis of S.suis.Researchers have reported that SLY-producing S.suis can penetrate the human brain microvascular endothelial cell monolayer,and such biochemical activity can be inhibited by SLY antibody.In addition,the incidence and prevalence of meningitis is closely related to the ability of bacterial secretion of SLY.Therefore,targeting SLY may represent a new stategy for treating S.suis infection.According to the phenotype of SLY function,hemolysis assay was used for the screen of SLY inhibitors,based on which morin was identified as effective SLY inhibitor by directly inhibiting SLY activity but not the expression of SLY.Furthermore,the addition of morin into the co-culture system of S.suis and host cells could significantly reduce the cellular damage mediated by S.suis.Finally,a mouse model of S.suis infection was established for the analysis of the treatment of morin on the infected mice.As expected,morin treatment significantly reduce the colonization of bacteria in brain tissue and the mortality of infected mice.In summary,our study establish that morin is a potential lead compound for S.suis infection by targeting SLY and this study also provide clues and experimental support for clinical research of new drugs against S.suis infection.