Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nat Commun. 2017 Jan 9;8:14023. doi: 10.1038/ncomms14023.
Pathogens use a variety of secreted and surface proteins to interact with and manipulate their hosts, but a systematic approach for identifying such proteins has been lacking. To identify these 'host-exposed' proteins, we used spatially restricted enzymatic tagging followed by mass spectrometry analysis of Caenorhabditis elegans infected with two species of Nematocida microsporidia. We identified 82 microsporidia proteins inside of intestinal cells, including several pathogen proteins in the nucleus. These microsporidia proteins are enriched in targeting signals, are rapidly evolving and belong to large Nematocida-specific gene families. We also find that large, species-specific families are common throughout microsporidia species. Our data suggest that the use of a large number of rapidly evolving species-specific proteins represents a common strategy for microsporidia to interact with their hosts. The unbiased method described here for identifying potential pathogen effectors represents a powerful approach to study a broad range of pathogens.
病原体利用各种分泌蛋白和表面蛋白与宿主相互作用并操纵宿主，但缺乏一种系统的方法来识别这些蛋白质。为了鉴定这些“暴露于宿主的”蛋白质，我们使用空间受限的酶标记，然后对感染两种 Nematocida 微孢子虫的秀丽隐杆线虫进行质谱分析。我们在肠细胞内鉴定了 82 种微孢子虫蛋白，包括几种核内病原体蛋白。这些微孢子虫蛋白富含靶向信号，进化迅速，属于大型 Nematocida 特异性基因家族。我们还发现，大型、特异性的家族在整个微孢子虫物种中都很常见。我们的数据表明，大量快速进化的物种特异性蛋白的使用代表了微孢子虫与宿主相互作用的一种常见策略。这里描述的用于鉴定潜在病原体效应物的无偏方法代表了一种研究广泛病原体的有力方法。
