Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.
J Infect Dis. 2012 Jul 15;206(2):292-301. doi: 10.1093/infdis/jis336. Epub 2012 May 2.
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.
α-溶血素（Hla）是一种自我组装的、形成通道的毒素，由金黄色葡萄球菌分泌，是动物模型中肺部、腹腔内、乳腺内和角膜感染发病机制的核心。在这项研究中，我们报告了黄芩苷（BAI），一种缺乏抗金黄色葡萄球菌活性的天然化合物，可以抑制 Hla 的溶血活性。通过分子动力学模拟和突变分析，我们进一步证明 BAI 结合到 Hla 中 Y148、P151 和 F153 的结合位点。这种结合抑制了七聚体的形成。此外，当添加到金黄色葡萄球菌培养物中时，BAI 可防止 Hla 介导的人肺泡上皮（A549）细胞损伤。体内研究进一步表明，BAI 可保护小鼠免受金黄色葡萄球菌肺炎的侵害。这些发现表明，BAI 通过一种干扰七聚体形成的新机制阻碍了 Hla 的细胞裂解活性，这可能导致开发针对金黄色葡萄球菌 Hla 的新型治疗方法。
