The Therapeutic Effect And Application Of Ginkgo Biloba Extract Against Streptococcus Suis Infection

Streptococcus suis(S. suis), an important zoonotic gram positive opportunistic bacteria, could cause meningitis, arthritis, endocarditis and septicemia in humans and animals, seriously threatening the development of swine industry and public health. To date, 35 different capsular types of S. suis have been described and serotype 2(SS2) is considered to be the most pathogenic as well as most prevalent capsular type in diseased pigs. Due to the multiple serotypes of S. suis, the prevention of vaccine maybe could not achieve the ideal results. Additionally, the development of drug resistance worsens the therapeutic effect of antibiotics, which calls for new strategies and agents for S. suis infection. In recent years, a variety of scientific reports have revealed that the pathogenicity of bacteria depend largely on the synthesized and secreted virulence factors. Thus, the therapeutic effect of antimicrobial agents is not only depending on the antibacterial activity but also the intervention effect of antimicrobial agents. Anti-virulence has been increasingly concerned by people.The pathogenicity of SS2 is closely related to the virulence factors of Sortase A and suilysin. The anchorage of surface proteins is mediated by Sortase A and suilysin, a pore-forming toxin, could lyse the targeted cells. Therefore, the inhibitors of Sortase A and suilysin have been identified by their function from Traditional Chinese Medicine and the results indicated that ginkgo biloba extract could inhibits the hemolytic activity of suilysin and the catalytic activity of Sortase A at the concentrations of 4-32 μg/m L. However, the synthesis of suilysin is not affected by ginkgo biloba extract. These above results suggest that ginkgo biloba extract represents a promising candidate for the development of agent against SS2 infection. The results from antibacterial activity test indicated that the MICs of ginkgo biloba extract against SS2 range 256 μg/m L to 1024 μg/m L, suggesting that ginkgo biloba extract has little antibacterial activity. Bactericidal activity test suggested that the MBCs of ginkgo biloba extract against SS2 are one to four times as much as MICs. Based on the fact that if MBC≥32 × MIC, the bacteria are resistant to tested agents, SS2 did not produce resistance to ginkgo biloba extract.To further analyze the effect of ginkgo biloba extract on the virulence of SS2 in vitro, we have determined the adhesion, invasion, cytotoxicity and translocation of SS2 with vascular endothelial cells b End.3 in the co-culture system of SS2 and b End.3. As expected, the addition of ginkgo biloba extract significantly inhibited the adhesion, invasion, cytotoxicity and translocation of SS2 with vascular endothelial cells b End.3 in the co-culture system of SS2 and b End.3. These results suggested that ginkgo biloba extract remarkably inhibit SS2 virulence in vitro and it may be a promising candidate for SS2 infection.Additionally, the experimental animal model(mice and swine) of SS2 infection was established to further analyze the mortality, bacterial concentrations in brain and clinical performance of infected animals treated with or without ginkgo biloba extract. Consistent with the results from cell infection, the inhibition of SS2 virulence by ginkgo biloba extract also occurred in vivo for both infected mice and infected swine.Taken together, ginkgo biloba extract, one of Traditional Chinese Medicine with little or even without antibacterial activity, could directly neutralize the function of suilysin and Sortase A. Furthermore, the virulence of SS2 in vitro and in vivo were both significantly inhibited in the presence of ginkgo biloba extract, which is due to the inhibition of the function of suilysin and Sortase A. Our study suggested that ginkgo biloba extractrepresents a promising candidate for the development of agent against SS2 infection with a novel strategy.