a State Key Laboratory of Electroanalytical Chemistry , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , People's Republic of China.
c Department of Food Quality and Safety , College of Food Science and Engineering, Jilin University , Changchun , People's Republic of China.
Emerg Microbes Infect. 2019;8(1):707-716. doi: 10.1080/22221751.2019.1617643.
() is one of the most serious human pathogens. α-Hemolysin (Hla) secreted by is a key toxin for various infections. We herein report that Honokiol, a natural plant polyphenol, inhibits the secretion and hemolytic activity of staphylococcal Hla with concomitant growth inhibition of and protection of -mediated cell injury within subinhibitory concentrations. In parallel, Honokiol attenuates the staphylococcal Hla-induced inflammatory response by inhibiting NLRP3 inflammasome activation and . Consequently, the biologically active forms of the inflammatory cytokines IL-1 and IL-18 are reduced significantly in response to Honokiol in mice infected with . Experimentally, we confirm that Honokiol binds to monomeric Hla with a modest affinity without impairing its oligomerization. Based on molecular docking analyses , we make a theoretical discovery that Honokiol is located outside of the triangular region of monomeric Hla. The binding model restricts the function of the residues related to membrane channel formation, which leads to the functional disruption of the assembled membrane channel. This research creates a new paradigm for developing therapeutic agents against staphylococcal Hla-mediated infections.
（金黄色葡萄球菌）是一种严重的人类病原体。金黄色葡萄球菌分泌的α-溶血素（Hla）是各种感染的关键毒素。本文报道，和厚朴酚是一种天然植物多酚，能够在亚抑菌浓度下抑制金黄色葡萄球菌 Hla 的分泌和溶血活性，同时抑制金黄色葡萄球菌的生长并保护其介导的细胞损伤。此外，和厚朴酚还通过抑制 NLRP3 炎性小体的激活来减轻金黄色葡萄球菌 Hla 诱导的炎症反应。因此，在金黄色葡萄球菌感染的小鼠中，和厚朴酚能显著减少炎性细胞因子 IL-1 和 IL-18 的生物活性形式。在实验中，我们证实和厚朴酚与单体 Hla 结合具有适度的亲和力，而不会损害其寡聚化。基于分子对接分析，我们做出了一个理论发现，即和厚朴酚位于单体 Hla 的三角形区域之外。该结合模型限制了与膜通道形成相关的残基的功能，从而导致组装的膜通道功能障碍。这项研究为开发针对金黄色葡萄球菌 Hla 介导的感染的治疗药物创造了一个新的范例。
