Wogonin attenuates the pathogenicity of Streptococcus pneumoniae by double‐target inhibition of Pneumolysin and Sortase A

Abstract

Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore‐forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface‐associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY‐mediated cell damage and reduced SrtA‐mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony‐forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF‐α, IL‐6 and IL‐1β in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection.

The Complete Assessment of Small Molecule and Peptidomimetic Inhibitors of Sortase A Towards Antivirulence Treatment

“…Taxifolin was also shown to be in vivo active in an MRSA‐induced pneumonia model in mice, where it significantly increased survival rate and decreased the amount of viable S. aureus in the lung tissue of the mice. Wogonin (Figure 6), a flavonoid widely found in traditional Chinese medicinal plants, was found to be able to inhibit the S. pneumoniae SrtA with an IC 50 of 185.7 μM [45] . Simultaneously, wogonin was able to target pneumolysin, which is a pore forming toxin that causes host tissue injury and inflammatory responses, leading to a dual effect where it prevents both biofilm formation and cell damage [46] .…”

“…Wogonin (Figure 6), a flavonoid widely found in traditional Chinese medicinal plants, was found to be able to inhibit the S. pneumoniae SrtA with an IC 50 of 185.7 μM. [45] Simultaneously, wogonin was able to target pneumolysin, which is a pore forming toxin that causes host tissue injury and inflammatory responses, leading to a dual effect where it prevents both biofilm formation and cell damage. [46] Wogonin was subsequently shown to reduce the mortality rate in pneumonia models of mice which were infected with S. pneumoniae, while also reducing levels of various inflammatory factors.…”