Apigenin and Ampicillin as Combined Strategy to Treat Severe Streptococcus suis Infection.

Hao Lu,Wenjia Lu,Xiaodan Li,Manli Liu,Chenchen Wang,Chen Tan,Gaoyan Wang,Zhaoyuan Wu,Wenqi Dong

doi:10.3390/molecules26071980

Abstract

As an important zoonotic pathogen, Streptococcus suis (S. suis) can cause a variety of diseases both in human and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which commonly appears in severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of host death. Therefore, it is urgent to find a new strategy to relieve the damage caused by STSLS. In this study, we found, for the first time, that apigenin, as a flavonoid compound, could combine with ampicillin to treat severe S. suis infection. Studies found that apigenin did not affect the growth of S. suis and the secretion of suilysin (SLY), but it could significantly inhibit the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. In cell assays, apigenin was found to have no significant toxic effects on effective concentrations, and have a good protective effect on S. suis-infected cells. More importantly, compared with the survival rate of S. suis-infected mice treated with only ampicillin, the survival rate of apigenin combined with an ampicillin-treated group significantly increased to 80%. In conclusion, all results indicate that apigenin in combination with conventional antibiotics can be a potential strategy for treating severe S. suis infection.

Highlights

S. suis can cause many disorders, such as septicemia, meningitis, arthritis, and endocarditis, in both humans and pigs and has a high mortality rate
The hemolytic activity of the supernatant from the coculture system of SC19 and apigenin (8 to 32 μg/mL) was significantly lower than that of the SC19 culture alone, which showed that apigenin decreased the hemolytic activity of the SC19 culture supernatant in a dose-dependent manner
The results showed that apigenin significantly inhibited the production of tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 in the supernatant of J774 cells infected with SS2 in a dose-dependent manner

Summary

Introduction

S. suis can cause many disorders, such as septicemia, meningitis, arthritis, and endocarditis, in both humans and pigs and has a high mortality rate. Since the first case was found in 1968, more than 1600 cases of human infection of S. suis have been reported [1]. S. suis is an emerging infectious pathogen. Among the known serotypes of Streptococcus suis, serotype 2 (SS2) is the most common serotype in pigs and humans, and it has been reported worldwide [3]. S. suis is a serious pathogen that causes meningitis in Vietnam, Thailand, and Hong Kong [4,5]. The survivors of meningitis caused by S. suis often have severe sequelae such as deafness [6]. In 2005, 215 human cases of S. suis were reported in Sichuan

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Discussion

Conclusion