Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions
Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions
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DOI：
10.1074/jbc.m308142200
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发表时间：
2003-11-14
影响因子：
4.8
通讯作者：
Aroian, RV
中科院分区：
文献类型：
--
作者：
Griffitts, JS;Huffman, DL;Aroian, RV
由细菌苏云金芽孢杆菌（Bacillus thuringiensis）制成的晶体（Cry）蛋白是专门针对昆虫和线虫的成孔毒素，并在世界各地用于杀死害虫。为了更好地了解成孔毒素如何与宿主相互作用，我们筛选了抵抗Cry蛋白中毒的秀丽隐杆线虫突变体。我们发现Cry毒素抗性涉及两个糖基转移酶基因bre-2和bre-4的丢失。这些糖基转移酶在肠中起作用，赋予对毒素的敏感性。此外，它们是活性毒素与肠细胞相互作用所必需的，这表明它们是毒素的寡糖受体。同样，bre-3抗性基因也是毒素与肠细胞相互作用所必需的。bre-3基因的克隆表明，该基因为C.果蝇eggh基因的同源物。这一鉴定是惊人的，因为先前鉴定的bre-5与果蝇brainiac（brn）具有同源性，并且egh-brn可能在果蝇上皮细胞中作为连续的糖基转移酶起作用。我们发现，与果蝇一样，bre-3和bre-5在C.优雅的bre-2和bre-4也是这条通路的一部分，从而延伸了这条通路。BRE-5编码C. elegans中优势的UDP-GlcNAc：Man GlcNAc转移酶活性。优美的对Cry毒素的抗性已经揭示了一种四组分糖基化途径，该途径在线虫和昆虫之间功能保守，并且为C.优雅的
Crystal (Cry) proteins made by the bacterium Bacillus thuringiensis are pore-forming toxins that specifically target insects and nematodes and are used around the world to kill insect pests. To better understand how pore-forming toxins interact with their host, we have screened for Caenorhabditis elegans mutants that resist Cry protein intoxication. We find that Cry toxin resistance involves the loss of two glycosyltransferase genes, bre-2 and bre-4. These glycosyltransferases function in the intestine to confer susceptibility to toxin. Furthermore, they are required for the interaction of active toxin with intestinal cells, suggesting they make an oligosaccharide receptor for toxin. Similarly, the bre-3 resistance gene is also required for toxin interaction with intestinal cells. Cloning of the bre-3 gene indicates it is the C. elegans homologue of the Drosophila egghead (egh) gene. This identification is striking given that the previously identified bre-5 has homology to Drosophila brainiac (brn) and that egh-brn likely function as consecutive glycosyltransferases in Drosophila epithelial cells. We find that, like in Drosophila, bre-3 and bre-5 act in a single pathway in C. elegans. bre-2 and bre-4 are also part of this pathway, thereby extending it. Consistent with its homology to brn, we demonstrate that C. elegans bre-5 rescues the Drosophila brn mutant and that BRE-5 encodes the dominant UDP-GlcNAc:Man GlcNAc transferase activity in C. elegans. Resistance to Cry toxins has uncovered a four component glycosylation pathway that is functionally conserved between nematodes and insects and that provides the basis of the dominant mechanism of resistance in C. elegans.