Subinhibitory concentrations of Honokiol reduce α-Hemolysin (Hla) secretion by Staphylococcus aureus and the Hla-induced inflammatory response by inactivating the NLRP3 inflammasome
Subinhibitory concentrations of Honokiol reduce α-Hemolysin (Hla) secretion by Staphylococcus aureus and the Hla-induced inflammatory response by inactivating the NLRP3 inflammasome
复制标题
亚抑制浓度的和厚朴酚可通过灭活 NLRP3 炎性体来减少金黄色葡萄球菌的 α-溶血素 (Hla) 分泌以及 Hla 诱导的炎症反应
DOI：
10.1080/22221751.2019.1617643
复制
发表时间：
2019-05-23
影响因子：
13.2
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Guo, Na;Liu, Zuojia;Wang, Jin
Staphylococcus aureus (S. aureus) is one of the most serious human pathogens. alpha-Hemolysin (Hla) secreted by S. aureus 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 S. aureus and protection of S. aureus-mediated cell injury within subinhibitory concentrations. In parallel, Honokiol attenuates the staphylococcal Hla-induced inflammatory response by inhibiting NLRP3 inflammasome activation in vitro and in vivo. Consequently, the biologically active forms of the inflammatory cytokines IL-1 beta and IL-18 are reduced significantly in response to Honokiol in mice infected with S. aureus. Experimentally, we confirm that Honokiol binds to monomeric Hla with a modest affinity without impairing its oligomerization. Based on molecular docking analyses in silico, 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.
