Isorhamnetin as a novel inhibitor of pneumolysin against Streptococcus pneumoniae infection in vivo/in vitro

The increasing incidence of Streptococcus pneumoniae (S. pneumoniae) infection severely threatened the global public heath, causing a significant fatality in immunocompromised hosts. Notably, pneumolysin (PLY) as a pore-forming cytolysin plays a crucial role in the pathogenesis of pneumococcal pneumonia and lung injury. In this study, a natural flavonoid isorhamnetin was identified as a PLY inhibition to suppress PLY-induced hemolysis by engaging the predicted residues and attenuate cytolysin PLY-mediated A549 cells injury. Underlying mechanisms revealed that PLY inhibitor isorhamnetin further contributed to decrease the formation of bacterial biofilms without affecting the expression of PLY. In vivo S. pneumoniae infection confirmed that the pathological injury of lung tissue evoked by S. pneumoniae was ameliorated by isorhamnetin treatment. Collectively, these results presented that isorhamnetin could inhibit the biological activity of PLY, thus reducing the pathogenicity of S. pneumoniae. In summary, our study laid a foundation for the feasible anti-virulence strategy targeting PLY, and provided a promising PLY inhibitor for the treatment of S. pneumoniae infection.

Automated summary

This study identified the natural flavonoid isorhamnetin as an inhibitor of PLY, which reduces the pathogenicity of S. pneumoniae. Isorhamnetin also decreases the formation of bacterial biofilms and attenuates PLY-mediated injury. In vivo experiments confirmed the efficacy of isorhamnetin in ameliorating lung tissue injury caused by S. pneumoniae.