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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >An engineered innate immune defense protects grapevines from Pierce disease
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An engineered innate immune defense protects grapevines from Pierce disease

机译:经过精心设计的先天免疫防御功能可以保护葡萄藤免受皮尔斯病的侵害

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We postulated that a synergistic combination of two innate immune functions, pathogen surface recognition and lysis, in a protein chimera would lead to a robust class of engineered antimicrobial therapeutics for protection against pathogens. In support of our hy pothesis, we have engineered such a chimera to protect against the Gram-negative Xylella fastidiosa (Xf), which causes diseases in multiple plants of economic importance. Here we report the design and delivery of this chimera to target the Xf subspecies fastidiosa (Xff), which causes Pierce disease in grapevines and poses a great threat to the wine-growing regions of California. One domain of this chimera is an elastase that recognizes and cleaves MopB, a conserved outer membrane protein of Xff. The second domain is a lytic peptide, cecro-pin B, which targets conserved lipid moieties and creates pores in the Xff outer membrane. A flexible linker joins the recognition and lysis domains, thereby ensuring correct folding of the individual domains and synergistic combination of their functions. The chimera trans-gene is fused with an amino-terminal signal sequence to facilitate delivery of the chimera to the plant xylem, the site of Xff colonization. We demonstrate that the protein chimera expressed in the xylem is able to directly target Xff, suppress its growth, and significantly decrease the leaf scorching and xylem clogging commonly associated with Pierce disease in grapevines. We believe that similar strategies involving protein chimeras can be developed to protect against many diseases caused by human and plant pathogens.
机译:我们假设在蛋白质嵌合体中两个先天免疫功能,病原体表面识别和裂解的协同组合将导致一类强大的工程化抗菌药物,以防御病原体。为了支持我们的假设,我们设计了这样一种嵌合体来预防革兰氏阴性的木霉(Xf),该病会在具有重要经济意义的多种植物中引起疾病​​。在这里,我们报道了针对Xf的Fastidiosa亚种(Xff)的这种嵌合体的设计和交付,Xf亚种在葡萄树上引起皮尔斯病,对加利福尼亚的葡萄酒产区构成了巨大威胁。这种嵌合体的一个结构域是一种弹性蛋白酶,可识别并切割MoffB(一种保守的Xff外膜蛋白)。第二个结构域是裂解肽cecro-pin B,其靶向保守的脂质部分并在Xff外膜上形成孔。灵活的接头将识别域和裂解域连接在一起,从而确保各个域的正确折叠以及它们功能的协同组合。将嵌合体转基因与氨基末端信号序列融合,以促进将嵌合体递送至植物木质部,即Xff定植位点。我们证明在木质部中表达的蛋白质嵌合体能够直接靶向Xff,抑制其生长并显着降低通常与葡萄皮尔斯病相关的叶子焦化和木质部堵塞。我们认为,可以开发出涉及蛋白质嵌合体的类似策略来预防人类和植物病原体引起的许多疾病。

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