Betulin attenuates pneumolysin-induced cell injury and DNA damage

Aims Pneumolysin, a pore-forming toxin, is an important virulence factor ofStreptococcus pneumoniaewith multiple biological activity, such as cell lysis and DNA damage. Thus, targeting this toxin is alternative strategy for the treatment ofS. pneumoniaeinfection. Methods and Results Haemolysin assay was performed to identify the potential PLY inhibitor. The mechanism by which betulin, a natural compound from birch bark, against PLY was determined via MICs determination, western blot analysis and oligomerization analysis. Cytotoxicity and Immunofluorescence assays were further used to evaluate the protection of betulin against PLY-induced cell injury and DNA damage. Here, betulin, a natural compound from birch bark, was indentified as an effective inhibitor of PLY. Importantly, at the concentrations required for such inhibition, betulin has no influence onS. pneumoniaeviability or PLY production. The interaction of betulin with PLY restrict the olgomerizaiton of this toxin and, thus, directly neutralizing the activity of PLY. Additionally, betulin treatment alleviate PLY induced cells injury and DNA damage in the co-culture system of PLY and A549 cells. Conclusions Betulin could be used as a promising leading compound againstS. pneumoniaevirulence by directly targeting PLY without antibacterial activity. Significance and Impact of the Study The results presented in this work provided a novel strategy and candidate forS. pneumoniaeinfection.

Automated summary

Betulin was identified as an effective inhibitor of pneumolysin without affecting Streptococcus pneumoniae viability, directly neutralizing its activity. These findings suggest betulin is a promising candidate for treating S. pneumoniae infection by targeting pneumolysin's virulence.