Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences.
Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences.
复制标题
拮抗真菌肠毒素与宿主的天然免疫防御系统在多个水平上相互作用。
DOI：
10.1371/journal.pgen.1009600
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发表时间：
2021-06
期刊：
影响因子：
4.5
通讯作者：
Ewbank JJ
中科院分区：
文献类型：
--
作者：
Zhang X;Harding BW;Aggad D;Courtine D;Chen JX;Pujol N;Ewbank JJ
动物和植物需要保护自己免受病原体的攻击。它们的防御机制推动了毒力机制的创新，导致宿主和病原体永无休止的共同进化循环。因此，充分了解宿主免疫力需要检查病原体的毒力策略。在这里，我们充分研究秀丽隐杆线虫的先天免疫系统的优势，剖析其天然真菌病原体锥孢德氏菌的两个毒力因子的作用。我们发现，这两种肠毒素有显着不同的影响时，单独表达在线虫表皮。一种是能够干扰宿主细胞生物学的各个方面，改变囊泡运输和阻止关键的STAT样转录因子STA-2激活防御性抗菌肽基因表达。第二个增加STA-2水平在细胞核中，修改核仁，并可能作为一个结果的主机监视机制，导致增加防御基因的表达。我们的研究结果突出了在共同进化的宿主和病原体之间的相互作用中发挥作用的非常复杂和潜在的拮抗机制。当病原真菌入侵动物时，它可以部署一系列令人眼花缭乱的分子武器：数百种蛋白质被直接注入宿主细胞，使真菌能够生长和繁殖。我们研究了一种简单的动物宿主，线虫C。线虫和它的天敌，真菌锥孢德氏锥孢霉，它具有大量的未表征的潜在“毒力因子”。在这里，我们只关注其中两种真菌蛋白质，称为肠毒素。通过在C.线虫，我们能够研究它们对宿主的特定影响，特别是它们改变宿主免疫防御的方式。这两种肠毒素的作用截然不同。一种阻断了蠕虫制造保护性抗菌肽的能力，而另一种实际上刺激了它们的生产。通过结合遗传学、生物化学和细胞生物学，我们揭示了这些拮抗作用的基础。每一种肠毒素都通过改变蠕虫生物学的不同方面发挥作用，尽管它们都干扰了宿主蛋白质的翻译。我们的研究结果提供了第一次深入了解肠毒素在这一特定的宿主-病原体斗争的分子和细胞基础。
Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens. When a pathogenic fungus invades an animal, it can deploy a bewildering battery of molecular weapons: hundreds of proteins are injected directly into the host’s cells to enable the fungus to grow and reproduce. We study a simple animal host, the nematode worm C. elegans and its natural enemy, the fungus Drechmeria coniospora, which has a large repertoire of uncharacterised potential “virulence factors”. Here, we focused on just two of these fungal proteins, called enterotoxins. By producing each enterotoxin inside the epidermis of C. elegans, we were able to study their specific effect on the host, and in particular on the way in which they altered the host’s immune defences. The two enterotoxins had strikingly different effects. One blocked the worms’ ability to make protective antimicrobial peptides, while the other actually stimulated their production. By combining genetics, biochemistry and cell biology, we uncovered the basis of these antagonistic actions. Each of the enterotoxins turned out to act by altering different aspects of the worms’ biology, despite both interfering with host protein translation. Our findings provide a first insight into the molecular and cellular basis of enterotoxins in this particular host-pathogen battle.
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影响因子：
3.7
作者：
Engelmann I;Griffon A;Tichit L;Montañana-Sanchis F;Wang G;Reinke V;Waterston RH;Hillier LW;Ewbank JJ
通讯作者：
Ewbank JJ
影响因子：
30.3
作者：
Dierking, Katja;Polanowska, Jolanta;Pujol, Nathalie
通讯作者：
Pujol, Nathalie
影响因子：
4.6
作者：
de Bekker C;Ohm RA;Evans HC;Brachmann A;Hughes DP
通讯作者：
Hughes DP
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias