Xiaoran Zhao, Hongen Li, Jianfeng Wang, Yan Guo, Bowen Liu, Xuming Deng,
and Xiaodi Niu
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L.,
J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin
University, Changchun, China (X.N.).
Abstract
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.
Chemicals VBS (purity>98.8%) was purchased from Chengdu Herbpurify CO., LTD (Chengdu, Sichuan, China)
