Bacillus thuringiensis targets the host intestinal epithelial junctions for successful infection of Caenorhabditis elegans
Bacillus thuringiensis targets the host intestinal epithelial junctions for successful infection of Caenorhabditis elegans
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苏云金芽孢杆菌以宿主肠上皮连接为目标，成功感染秀丽隐杆线虫
DOI：
10.1111/1462-2920.14528
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发表时间：
2019
影响因子：
5.1
通讯作者：
Peng Donghai
中科院分区：
文献类型：
--
作者：
Wan Liting;Lin Jian;Du Hongwen;Zhang Yulan;Bravo Alej;ra;Soberon Mario;Sun Ming;Peng Donghai
致病菌使用不同的策略来感染宿主，包括同时产生成孔毒素和几种可能协同其致病作用的毒力因子。然而，人们对致病菌如何突破宿主肠道屏障知之甚少。秀丽隐杆线虫中苏云金芽孢杆菌 (Bt) 细菌的感染周期是研究感染过程早期阶段的强大模型系统。 Bt 在孢子形成阶段产生 Cry 成孔毒素，这是其发病机制中的关键毒力因子。在这项研究中，我们发现 Bt 会破坏 C 的肠上皮连接。 elegansat 能够在感染的早期阶段使 Bt 细菌在蠕虫体内完成其生命周期。我们进一步证实，营养性 Bt 细胞会触发由 PlcR 调节器激活的群体感应反应，从而产生不同的毒力因子，例如金属蛋白酶 ColB 和 Bmp1，除了 Cry 毒素之外，这些毒力因子也是破坏线虫上皮连接所必需的，从而导致有效的细菌宿主感染和线虫死亡。我们的工作为 Bt 的发病机制提供了新的见解，并强调了破坏宿主上皮连接对于成功感染的重要性。其他病原体与宿主的相互作用也可以使用类似的机制，因为上皮连接是从昆虫到哺乳动物的保守结构。
Pathogenic bacteria use different strategies to infect their hosts, including the simultaneous production of pore forming toxins and several virulence factors that may synergize their pathogenic effects. However, how the pathogenic bacteria are able to break out the host intestinal barrier is poorly understood. The infectious cycle ofBacillus thuringiensis(Bt) bacterium inCaenorhabditis elegansis a powerful model system to study the early stages of the infection process. Bt produces Cry pore‐forming toxins during the sporulation phase that are key virulence factors involved in its pathogenesis. In this study, we show that Bt disrupts the intestinal epithelial junctions ofC. elegansat early stages of infection allowing Bt bacterium to complete its life cycle in the worm. We further confirmed that the vegetative Bt cells trigger a quorum sensing response that is activated by PlcR regulator, resulting in production of different virulence factors, such as the metalloproteinases ColB and Bmp1, that besides Cry toxins are necessary to disrupt the nematode epithelial junctions causing efficient bacterial host infection and death of the nematode. Our work provides new insights into the pathogenesis of Bt and highlights the importance of breaking down host epithelial junctions for a successful infection. A similar mechanism could be used by other pathogen‐host interactions since epithelial junctions are conserved structures from insects to mammals.