Betulin efficiently suppresses the process of an experimental Listeria monocytogenes infection as an antagonist against listeriolysin O
Betulin efficiently suppresses the process of an experimental Listeria monocytogenes infection as an antagonist against listeriolysin O
复制标题
作为李斯特菌溶血素 O 的拮抗剂，桦木醇可有效抑制实验性单核细胞增生李斯特菌感染的过程。
DOI：
10.1016/j.fitote.2019.104409
复制
发表时间：
2019-11-01
期刊：
影响因子：
3.4
通讯作者：
Feng, Haihua
中科院分区：
文献类型：
--
作者：
Lu, Gejin;Xu, Lei;Feng, Haihua
单核细胞增生李斯特菌（Listeria monocytogenes，Lm）是一种广泛存在的食源性胞内病原体，其侵入多种细胞，导致流产和严重的人类疾病。在内化到宿主细胞中后，成孔溶细胞素β-溶血素O（LLO）破坏吞噬体，这使得细菌能够存活并定殖细胞质，从而为细菌提供感染邻近细胞的机会。桦木醇是从桦树皮中提取的天然化合物，具有多种药理活性。在这里，我们表明，LLO诱导的兔红细胞溶解在体外抑制预孵育白桦脂醇，抑制寡聚化过程。用人单核细胞巨噬细胞进行的感染性测定表明，桦木醇显着保护细胞免受LM诱导的细胞损伤。此外，Balb/c小鼠进行全身感染，白桦脂醇给药明显抑制感染小鼠的器官损伤和肝、脾中的细菌负荷。总之，白桦脂醇在体外明显抑制Lm诱导的细胞损伤，并通过抗病毒作用保护体内免受感染。我们的研究结果表明，白桦脂醇作为一种新的候选人，通过靶向LLO，并强调了潜在的天然产物为基础的药物被应用于治疗病原性感染。
Listeria monocytogenes (Lm) is a widespread foodborne intracellular pathogen that invades a variety of cells, causing abortions and severe human diseases. After internalization into host cells, pore-forming cytolysin listeriolysin O (LLO) disrupts the phagosome, which allows the bacterium to survive and colonize the cytoplasm, providing the bacterium the chance to infect neighboring cells. Betulin is an extracted natural compound from birch bark with diverse pharmacological activities. Here, we showed that LLO-induced rabbit red blood cell lysis in vitro was inhibited by preincubation with betulin, which suppressed the oligomerization process. Infectious assays performed with human monocyte macrophages indicated that betulin significantly protected cells against Lm-induced cell injury. In addition, Balb/c mice were used to perform a general infection, and betulin administration obviously inhibited organ damage and bacterial burden in livers and spleens of infected mice. In conclusion, betulin obviously inhibited Lm-induced cell injury in vitro and protected against infection in vivo through an antivirulence effect. Our results showed betulin as a new candidate against listeriosis by targeting LLO and highlight the potential of natural product-based medicine to be applied in the treatment of pathogenic infections.