A proteomics approach reveals molecular manipulators of distinct cellular processes in the salivary glands of Glossina m. morsitans in response to Trypanosoma b. brucei infections.
A proteomics approach reveals molecular manipulators of distinct cellular processes in the salivary glands of Glossina m. morsitans in response to Trypanosoma b. brucei infections.
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DOI：
10.1186/s13071-016-1714-z
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发表时间：
2016-08-02
影响因子：
3.2
通讯作者：
Abd-Alla AM
中科院分区：
文献类型：
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作者：
Kariithi HM;Boeren S;Murungi EK;Vlak JM;Abd-Alla AM
Glossina m. morsitans是布氏锥虫群的主要载体，布氏锥虫群是非洲锥虫病的病原体之一。寄生虫在采采蝇媒介的唾液腺（SG）中经历后循环发生，即转化为可感染果蝇的后循环锥鞭毛体（MT）寄生虫。由于MT-寄生虫在很大程度上是不可培养的体外，信息的分子过程中，促进metacyclogenesis是很少的。为了弥补这一知识空白，我们采用串联质谱法研究了寄生（T。B.感染布氏杆菌）和未感染布氏杆菌的SG。M. Morsitans。我们将识别的蛋白质注释到基因本体中，并在蛋白质-蛋白质相互作用（PPI）网络中映射上调和下调的蛋白质。我们鉴定了361种宿主蛋白，其中76.6%（n = 276）和22.3%（n = 81）在寄生的SG中与未寄生的SG相比分别上调和下调。虽然32种蛋白质被显著上调（> 10倍），但只有唾液分泌的腺苷被显著下调。在显著上调的蛋白质中，存在与血液喂养、免疫、细胞增殖、稳态、细胞骨架运输和蛋白质周转调节相关的蛋白质。显著上调的蛋白质形成PPI网络中的主要枢纽，包括Ras/MAPK和Ca 2 +/cAMP信号通路、泛素-蛋白酶体系统和线粒体呼吸链的关键调节因子。此外，我们确定了158锥虫特异性蛋白质，其中值得注意的是GPI锚定的表面糖蛋白，动质体钙蛋白酶，过氧化物酶，逆转录转座子宿主斑点多基因和分子伴侣的家庭中的蛋白质。虽然免疫相关的锥虫蛋白质的代表性过高，膜转运蛋白和蛋白质参与翻译抑制（如核糖体蛋白）的代表性不足，可能会让人联想到生长停滞的MT-寄生虫。我们的数据暗示了显著上调的蛋白质作为不同细胞过程的操纵者响应T。B.布氏杆菌感染，潜在地准备MT-寄生虫入侵和逃避哺乳动物宿主的免疫防御。我们讨论了潜在的策略，以利用我们的研究结果在增强锥虫不应性或减少采采蝇载体的载体能力。本文的在线版本（doi：10.1186/s13071-016-1714-z）包含补充材料，可供授权用户使用。
Glossina m. morsitans is the primary vector of the Trypanosoma brucei group, one of the causative agents of African trypanosomoses. The parasites undergo metacyclogenesis, i.e. transformation into the mammalian-infective metacyclic trypomastigote (MT) parasites, in the salivary glands (SGs) of the tsetse vector. Since the MT-parasites are largely uncultivable in vitro, information on the molecular processes that facilitate metacyclogenesis is scanty. To bridge this knowledge gap, we employed tandem mass spectrometry to investigate protein expression modulations in parasitized (T. b. brucei-infected) and unparasitized SGs of G. m. morsitans. We annotated the identified proteins into gene ontologies and mapped the up- and downregulated proteins within protein-protein interaction (PPI) networks. We identified 361 host proteins, of which 76.6 % (n = 276) and 22.3 % (n = 81) were up- and downregulated, respectively, in parasitized SGs compared to unparasitized SGs. Whilst 32 proteins were significantly upregulated (> 10-fold), only salivary secreted adenosine was significantly downregulated. Amongst the significantly upregulated proteins, there were proteins associated with blood feeding, immunity, cellular proliferation, homeostasis, cytoskeletal traffic and regulation of protein turnover. The significantly upregulated proteins formed major hubs in the PPI network including key regulators of the Ras/MAPK and Ca2+/cAMP signaling pathways, ubiquitin-proteasome system and mitochondrial respiratory chain. Moreover, we identified 158 trypanosome-specific proteins, notable of which were proteins in the families of the GPI-anchored surface glycoproteins, kinetoplastid calpains, peroxiredoxins, retrotransposon host spot multigene and molecular chaperones. Whilst immune-related trypanosome proteins were over-represented, membrane transporters and proteins involved in translation repression (e.g. ribosomal proteins) were under-represented, potentially reminiscent of the growth-arrested MT-parasites. Our data implicate the significantly upregulated proteins as manipulators of diverse cellular processes in response to T. b. brucei infection, potentially to prepare the MT-parasites for invasion and evasion of the mammalian host immune defences. We discuss potential strategies to exploit our findings in enhancement of trypanosome refractoriness or reduce the vector competence of the tsetse vector. The online version of this article (doi:10.1186/s13071-016-1714-z) contains supplementary material, which is available to authorized users.