Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin.

Yanyan Zhang,Xiangru Wang,Manli Liu,Linlin Hu,Yongwei Zhu,Huanchun Chen,Anding Zhang,Pei Li,Chen Tan,Bingbing Zong

doi:10.3389/fmicb.2018.01723

Abstract

Streptococcus suis serotype 2 is a serious zoonotic pathogen and has attracted worldwide attention since the first human case was reported in Denmark in 1968. Some virulence factors have been reported to be involved in the pathogenesis of the infection caused by Streptococcus suis serotype 2, and then novel strategies to identify some anti-virulence compounds which can effectively inhibit the pathogenic bacterial infection have recently been reported. Suilysin is an essential virulence factor for Streptococcus suis serotype 2 since it creates pores in the target cells membranes, which aids bacterial colonization. The important role of suilysin in the virulence of Streptococcus suis serotype 2 renders it an ideal target for designing novel anti-virulence therapeutics. We find that fisetin, as a natural flavonoid, is a potent antagonist against suilysin-mediated hemolysis. The aim of this study is to evaluate the effect of fisetin on the hemolytic activity of suilysin from Streptococcus suis serotype 2. Fisetin is found to significantly inhibit the hemolytic activity of suilysin. Within the range of effective concentrations, fisetin does not influence the growth of Streptococcus suis serotype 2 and the expression of suilysin protein. In vitro, fisetin effectively inhibits the death of macrophages (J774A.1 and RAW264.7) infected with Streptococcus suis serotype 2 by weakening intracellular bacterial multiplication. Animal model experiment shows that fisetin effectively improves the survival rate of animals infected with Streptococcus suis serotype 2. Our findings suggest that fisetin could be used as an antitoxin against suilysin and be developed into a promising therapeutic candidate for treating Streptococcus suis serotype 2 infection.

Highlights

Streptococcus suis (S. suis) is a common pathogen which can cause a variety of diseases, including meningitis, arthritis, septicemia, pneumonia, and endocarditis (Staats et al, 1997; Sriskandan and Slater, 2006; Kerdsin et al, 2016)
We found that fisetin (Figure 1B), a dietary flavonoid found in vegetables and fruits, significantly inhibited the hemolytic activity of a culture supernatant of SC19 in the stationary phase (Figure 1C)
Our further study found that the hemolytic activities of suilysin protein in the culture supernatant of SC19 were remarkably decreased in a dose-dependent manner after its coculture with fisetin

Summary

Introduction

Streptococcus suis (S. suis) is a common pathogen which can cause a variety of diseases, including meningitis, arthritis, septicemia, pneumonia, and endocarditis (Staats et al, 1997; Sriskandan and Slater, 2006; Kerdsin et al, 2016). These diseases cause a severe economic loss to the swine industry worldwide and pose a threat to human health. More than 1642 cases of S. suis human infection have been reported worldwide (Guillaume et al, 2014)

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