Fisetin Lowersserotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin.
Front Microbiol. 2018 ;9:1723. Epub 2018 Jul 30. PMID: 30105012
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 byserotype 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 forserotype 2 since it creates pores in the target cells membranes, which aids bacterial colonization. The important role of suilysin in the virulence ofserotype 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 fromserotype 2. Fisetin is found to significantly inhibit the hemolytic activity of suilysin. Within the range of effective concentrations, fisetin does not influence the growth ofserotype 2 and the expression of suilysin protein., fisetin effectively inhibits the death of macrophages (J774A.1 and RAW264.7) infected withserotype 2 by weakening intracellular bacterial multiplication. Animal model experiment shows that fisetin effectively improves the survival rate of animals infected withserotype 2. Our findings suggest that fisetin could be used as an antitoxin against suilysin and be developed into a promising therapeutic candidate for treatingserotype 2 infection.