Cortex Cercis chinensis Granules Attenuate Streptococcus pneumoniae Virulence by Targeting Pneumolysin

Pore-forming toxins produced by bacteria are some of the most important molecular weapons for bacterial virulence. Pneumolysin (PLY) is a pore-forming toxin secreted by Streptococcus pneumoniae (S. pneumoniae) and plays a vital role in the spread, colonization, and invasion of this bacterium in the host, indicating that PLY is a promising target for developing treatments against S. pneumoniae infection. In this study, Cortex Cercis chinensis granules (CCCGs), a prescription drug on the market, were shown to inhibit the pore-forming activity of PLY and protect against PLY-mediated cell hemolysis and A549 cell death without antibacterial activity or inhibition of PLY production. In addition, CCCG treatment inhibited the oligomerization of PLY. Animal experiments showed that CCCGs can reduce the death of mice infected with S. pneumoniae, the degree of pathological damage to the lungs, and the levels of TNF-α and IL-6 in the lungs. In summary, our results demonstrated that CCCGs, a marketed Chinese medicine, inhibit PLY activity and subsequently attenuate S. pneumoniae virulence, which would offer a novel strategy for fighting S. pneumoniae infection and a new use for CCCGs.