Protective effect of tanshinone IIA against Listeria monocytogenes infection in vitro and in vivo

Listeriolysin O (LLO) is a vital virulence factor for the intracellular replication and pathogenesis of Listeria monocytogenes. The search for an effective LLO activity inhibitor as an alternative approach for the treatment of L. monocytogenes infection has attracted great attention. Tanshinone IIA (Tan IIA) is a bioactive compound in the traditional Chinese medicine "Danshen". In this study, the protective effect of Tan IIA against L. monocytogenes infection was investigated using hemolysis test, LDH release method, oligomerization assay and molecular dynamics simulation in combination with in vivo mouse experiment. Tan IIA significantly inhibited the pore-forming activity of LLO by forming a stable LLO - Tan IIA complex. Meanwhile, Tan IIA concentration-dependently decreased the cytotoxicity of L. monocytogenes toward J774 and BeWo cells with the inhibitory rates being 41.3% and 54.5% at concentration of 8 µg/mL, respectively. Furthermore, the intracellular growth of L. monocytogenes was also inhibited by Tan IIA in an LLO-dependent manner. Of note, Tan IIA (80 mg/kg) protected mice against L. monocytogenes infections with the increased survival rate of 26.7%, reduced bacterial loads, alleviated tissue damages, and diminished inflammation. In conclusion, Tan IIA might be a promising anti-virulence candidate for the treatment of L. monocytogenes infection.