Hebert Francois Olivier, Phelps Luke, Samonte Irene, Panchal Mahesh, Grambauer Stephan, Barber Iain, Kalbe Martin, Landry Christian R, Aubin-Horth Nadia
Institut de Biologie Intégrative et des Systèmes (IBIS), Département de Biologie, Université Laval, Pavillon Charles-Eugènes-Marchand, Québec, G1V 0A6, Canada.
Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str 2, 24306, Ploen, Germany.
Parasit Vectors. 2015 Apr 15;8:225. doi: 10.1186/s13071-015-0834-1.
Endoparasites with complex life cycles are faced with several biological challenges, as they need to occupy various ecological niches throughout their development. Host phenotypes that increase the parasite's transmission rate to the next host have been extensively described, but few mechanistic explanations have been proposed to describe their proximate causes. In this study we explore the possibility that host phenotypic changes are triggered by the production of mimicry proteins from the parasite by using an ecological model system consisting of the infection of the threespine stickleback (Gasterosteus aculeatus) by the cestode Schistocephalus solidus.
Using RNA-seq data, we assembled 9,093 protein-coding genes from which ORFs were predicted to generate a reference proteome. Based on a previously published method, we built two complementary analysis pipelines to i) establish a general classification of protein similarity among various species (pipeline A) and ii) identify candidate mimicry proteins showing specific host-parasite similarities (pipeline B), a key feature underlying the possibility of molecular mimicry.
Ninety-four tapeworm proteins showed high local sequence homology with stickleback proteins. Four of these candidates correspond to secreted or membrane proteins that could be produced by the parasite and eventually be released in or be in contact with the host to modulate physiological pathways involved in various phenotypes (e.g. behaviors). One of these candidates belongs to the Wnt family, a large group of signaling molecules involved in cell-to-cell interactions and various developmental pathways. The three other candidates are involved in ion transport and post-translational protein modifications. We further confirmed that these four candidates are expressed in three different developmental stages of the cestode by RT-PCR, including the stages found in the host.
In this study, we identified mimicry candidate peptides from a behavior-altering cestode showing specific sequence similarity with host proteins. Despite their potential role in modulating host pathways that could lead to parasite-induced phenotypic changes and despite our confirmation that they are expressed in the developmental stage corresponding to the altered host behavior, further investigations will be needed to confirm their mechanistic role in the molecular cross-talk taking place between S. solidus and the threespine stickleback.
具有复杂生命周期的内寄生虫面临着诸多生物学挑战，因为它们在整个发育过程中需要占据不同的生态位。已广泛描述了能提高寄生虫向下一宿主传播率的宿主表型，但很少有机制性解释来阐述其直接原因。在本研究中，我们利用由绦虫固着裂头绦虫感染三刺鱼（Gasterosteus aculeatus）组成的生态模型系统，探讨宿主表型变化是否由寄生虫产生的模拟蛋白引发。
利用RNA测序数据，我们组装了9093个蛋白质编码基因，从中预测开放阅读框以生成参考蛋白质组。基于先前发表的方法，我们构建了两个互补的分析流程，以i）建立不同物种间蛋白质相似性的一般分类（流程A），以及ii）识别显示特定宿主 - 寄生虫相似性的候选模拟蛋白（流程B），这是分子模拟可能性的一个关键特征。
94种绦虫蛋白与三刺鱼蛋白显示出高度的局部序列同源性。这些候选蛋白中有4种对应于可能由寄生虫产生并最终释放到宿主中或与宿主接触以调节参与各种表型（如行为）的生理途径的分泌蛋白或膜蛋白。其中一个候选蛋白属于Wnt家族，这是一大类参与细胞间相互作用和各种发育途径的信号分子。其他三个候选蛋白参与离子转运和蛋白质翻译后修饰。我们通过逆转录聚合酶链反应进一步证实这四种候选蛋白在绦虫的三个不同发育阶段表达，包括在宿主体内发现的阶段。
在本研究中，我们从一种改变行为的绦虫中鉴定出与宿主蛋白具有特定序列相似性的模拟候选肽。尽管它们可能在调节宿主途径中发挥作用，从而导致寄生虫诱导的表型变化，并且我们证实它们在与宿主行为改变相对应的发育阶段表达，但仍需要进一步研究来证实它们在固着裂头绦虫和三刺鱼之间发生的分子相互作用中的机制作用。
