Silibinin attenuates Streptococcus suis serotype 2 virulence by targeting suilysin

Abstract

Aims:To determine the antivirulence properties of silibinin against suilysin (SLY), a virulence factor of Streptococcus suis serotype 2 (SS2) that plays an important role in the pathogenesis of S. suis infection and its protective effect against SS2 infection in a mouse model. Methods and Results: Susceptibility testing, haemolysis assay and Western blot assays were employed to evaluate the performance of silibinin on SLY poreforming activity. Cytotoxicity assays and mouse infection tests were also performed to determine the efficacy of silibinin against SS2 infection. The results showed that silibinin, a flavonoid with little anti-S. suis activity, was identified to be a potent antagonist of SLY-mediated haemolysis through the inhibition of its oligomerization. Treatment with silibinin reduced S. suisinduced cytotoxicity in macrophages (J774 cells). In addition, S. suis-infected mice that received silibinin showed a lower bacterial burden. Conclusions: Our results demonstrated that silibinin is a promising candidate for the development of antivirulence therapeutic agents to treat S. suis infections. Significance and Impact of the Study: The antivirulent property of silibinin against SS2 by targeting SLY provides the possibility for the future pharmaceutical application of silibinin to prevent and treat S. suis infection.

Acquiring high expression of suilysin enable non-epidemic Streptococccus suis to cause streptococcal toxic shock-like syndrome (STSLS) through NLRP3 inflammasome hyperactivation

“…Furthermore, the present study also indicated that the hemolytic activity of SLY was responsible for STSLS, because the overexpression of mutant SLY into ST1 strain could not cause STSLS (Figure 4). This might be the reason why so many potential drugs targeting SLY could attenuate pathogenicity of the epidemic S. suis [41][42][43][44][45][46]. In conclusion, the present study demonstrated that the overexpression of functional SLY but not mutant SLY in ST1 strain is sufficient for causing STSLS.…”

“…Furthermore, the present study also indicated that the hemolytic activity of SLY was responsible for STSLS, because the overexpression of mutant SLY into ST1 strain could not cause STSLS ( Figure 4 ). This might be the reason why so many potential drugs targeting SLY could attenuate pathogenicity of the epidemic S. suis [ 41–46 ].…”

Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca

“…Another study by Kumbar et al [ 31 ], showed that curcumin diminished the virulence of Porphyromonas gingivalis by reducing the expression of virulence factors genes. Also, Shen et al [ 32 ], showed that silibinin, a flavonoid that is isolated from S. marianum , reduced the virulence of Streptococcus suis serotype 2. The decrease in the expression of virulence genes may be related to the effect of the tested compounds on QS genes, which play an important role in regulating other bacterial factors such as pathogenicity, biofilm production, and secretion systems [ 33 ].…”

Antimicrobial compounds from an FDA-approved drug library with activity against Streptococcus suis

“…suis is of importance. Recently, a study was performed by screening inhibitors against the vital virulence factor suilysin, which showed that compounds including amentoflavone, silibinin and fisetin inhibited the activity of suilysin effectively (Shen et al, 2018, 2019; Zhang et al, 2018). However, due to lack of data on toxicology and pharmacokinetic evaluation about these compounds, whether they can be finally approved for clinical uses remains a question.…”