Pneumolysin (PLY), an essential virulence factor of Streptococcus pneumoniae (pneumococcus), can penetrate the physical defenses of the host and possesses inflammatory properties. The vital role PLY plays in pneumococcus pathogenesis makes this virulence factor one of the most promising targets for the treatment of pneumococcal infection. Verbascoside (VBS) is an agent that does not exhibit bacteriostatic activity but has been shown to inhibit PLY-mediated cytotoxicity. The results from molecular dynamics simulations and mutational analysis indicated that VBS binds to the cleft between domains 3 and 4 of PLY, thereby blocking PLY’s oligomerization and counteracting its hemolytic activity. Moreover, VBS can effectively alleviate PLY-mediated human alveolar epithelial (A549) cell injury, and treatment with VBS provides significant protection against lung damage and reduces mortality in a pneumococcal pneumonia murine model. Our results demonstrate that VBS is a strong candidate as a novel therapeutic in the treatment of Streptococcus pneumoniae infection.
Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers
버바스코사이드가 폐렴구균 폐렴을 완화시키는 방법은 폐렴리신 올리고머를 감소시키는 것입니다.
[Category] 폐렴구균 감염증,
[Article Type] journal-article
[Source] pubmed
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