Listeria monocytogenes (Lm) is a widespread foodborne intracellular pathogen that invades a variety of cells, causing abortions and severe human diseases. After internalization into host cells, pore-forming cytolysin listeriolysin O (LLO) disrupts the phagosome, which allows the bacterium to survive and colonize the cytoplasm, providing the bacterium the chance to infect neighboring cells. Betulin is an extracted natural compound from birch bark with diverse pharmacological activities. Here, we showed that LLO-induced rabbit red blood cell lysis in vitro was inhibited by preincubation with betulin, which suppressed the oligomerization process. Infectious assays performed with human monocyte macrophages indicated that betulin significantly protected cells against Lm-induced cell injury. In addition, Balb/c mice were used to perform a general infection, and betulin administration obviously inhibited organ damage and bacterial burden in livers and spleens of infected mice. In conclusion, betulin obviously inhibited Lm-induced cell injury in vitro and protected against infection in vivo through an antivirulence effect. Our results showed betulin as a new candidate against listeriosis by targeting LLO and highlight the potential of natural product-based medicine to be applied in the treatment of pathogenic infections.
Keywords: Anti-virulence; Betulin; Drug-resistance; LLO; Listeria monocytogenes.
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