Shikonin alleviates the biotoxicity produced by pneumococcal pneumolysin

Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that can cause severe infections in humans. Pneumolysin (PLY) is an important virulence trait of S. pneumoniae and has cytotoxicity, genotoxicity and pro-inflammatory activity; it is essential for the pathogenesis of S. pneumoniae pneumonia and is an anti-virulence target of small molecule drug development. The treatment options for this microbe were limit due to the ubiquitous antibiotic resistance; therefore, new drugs and treatment strategies are needed. Shikonin was selected by drug screening based on haemolysis assays, and its mechanism of suppressing PLY toxicity was determined by oligomerization assay. Meanwhile, the in vitro cell viability assays and in vivo experiments were performed to explore the capability of shikonin to protect cells and tissue from S. pneumoniae-mediated damage. Shikonin was found to significantly decrease PLY-induced haemolytic activity, cytotoxicity and genotoxicity via lessening the formation of oligomers; moreover, the agent can reduce the mortality of mice caused by lethal pneumonia and mitigate the injury of target organs as well. We suggest that shikonin could be a potent candidate for a novel therapeutic or auxiliary substance in the treatment of infections encountering insufficient vaccines and antimicrobial resistance to traditional antibiotics.