黄芩苷可通过抑制溶血素的细胞溶解活性而保护小鼠避免发生金黄色葡萄球菌肺炎
Key Laboratory of Zoonosis, Ministry of Education, Jilin University, Xi'an Rd 5333, Changchun 130062, China
α-Hemolysin (Hla) is a self-assembling, channel-forming toxin that is secreted by Staphylococcus aureus and is central to the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections in animal models. In this study, we report that baicalin (BAI), a natural compound that lacks anti-S. aureus activity, could inhibit the hemolytic activity of Hla. Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that BAI binds to the binding sites of Y148, P151, and F153 in the Hla. This binding interaction inhibits heptamer formation. Furthermore, when added to S. aureus cultures, BAI prevents Hla-mediated human alveolar epithelial (A549) cell injury. In vivo studies further demonstrated that BAI protects mice from S. aureus pneumonia. These findings indicate that BAI hinders the cell lysis activity of Hla through a novel mechanism of interrupting the formation of heptamer, which may lead to the development of novel therapeutics that aim against S. aureus Hla. © 2012 The Author.
Qiu, J.; Key Laboratory of Zoonosis, Ministry of Education, Jilin University, Xi'an Rd 5333, Changchun 130062, China; email: dengxm@jlu.edu.cn
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来源: Scopus
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