Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling.
Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling.
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DOI：
10.1371/journal.pntd.0000410
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发表时间：
2009
影响因子：
3.8
通讯作者：
Nutman TB
中科院分区：
文献类型：
--
作者：
Bennuru S;Semnani R;Meng Z;Ribeiro JM;Veenstra TD;Nutman TB
相对而言，人们对与人类宿主相互作用的丝虫蛋白质知之甚少。尽管丝虫基因组最近已经完成，但蛋白质谱仅限于少数重组体或纯化的感兴趣蛋白质。在这里，我们描述了一个大规模的蛋白质组学分析，采用微毛细管反相液相色谱-串联质谱法，以确定排泄分泌（ES）产品的L3，L3至L4蜕皮ES，成年男性，成年女性，和微丝蚴阶段的丝虫寄生虫马来丝虫。成年男性，成年女性，微丝蚴（Mf），L3和蜕皮L3幼虫的ES产物的分析确定了852个蛋白质。注释表明，在研究的每个阶段的功能和组分分布是非常相似的，但是，MF贡献了较高的比例，确定的蛋白质的总数比其他阶段。在ES中鉴定的852种蛋白质中，只有229种在现有数据库中具有先前的确认表达序列标签（EST）。此外，该分析能够确认从应用于B的基因预测算法推断的274种“假设”蛋白质的存在。马来人（Bm）基因组。毫不奇怪，Signal IP和/或SecretomeP 2.0分析预测这些“假设”蛋白质中的大多数（160/274）是分泌的。主要感兴趣的是丰富的先前表征的免疫调节蛋白，如ES-62（亮氨酰氨基肽酶），MIF-1，SERPIN，谷胱甘肽过氧化物酶，和半乳糖凝集素在微丝蚴（和MF含成年女性）的ES相比，成年男性。此外，搜索ES蛋白质谱对沃尔巴克氏体数据库导致90沃尔巴克氏体特异性蛋白质的鉴定，其中大多数是代谢酶，尚未被证明是免疫原性的。这种蛋白质组学分析扩展了我们对ES的了解，并提供了对宿主-寄生虫相互作用的深入了解。由线虫寄生虫马来丝虫和班氏吴策线虫引起的人类淋巴丝虫病是热带国家关注的一个主要原因。几十年来的研究已经确定了这些寄生虫的各种蛋白质，这些蛋白质突出了它们在宿主-寄生虫相互作用以及可能的化疗和预防干预中的作用。寄生虫基因组的可用性有助于鉴定寄生虫中可能与宿主相互作用的所有蛋白质。在这项研究中，我们试图确定排泄分泌蛋白的各个阶段的寄生虫，可以保持在体外有限的时间内利用高通量蛋白质组学方法。我们观察并报告，寄生虫消耗资源分泌出各种分子，它们利用这些分子来逃避宿主免疫系统并调节其反应。此外，这项研究还提供了预测的假设蛋白质是真正的蛋白质的信息，从而对宿主-寄生虫相互作用的更好的理解的排泄分泌蛋白的目录。
Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES) products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf), L3, and molting L3 larvae identified 852 proteins. Annotation suggests that the functional and component distribution was very similar across each of the stages studied; however, the Mf contributed a higher proportion to the total number of identified proteins than the other stages. Of the 852 proteins identified in the ES, only 229 had previous confirmatory expressed sequence tags (ESTs) in the available databases. Moreover, this analysis was able to confirm the presence of 274 “hypothetical” proteins inferred from gene prediction algorithms applied to the B. malayi (Bm) genome. Not surprisingly, the majority (160/274) of these “hypothetical” proteins were predicted to be secreted by Signal IP and/or SecretomeP 2.0 analysis. Of major interest is the abundance of previously characterized immunomodulatory proteins such as ES-62 (leucyl aminopeptidase), MIF-1, SERPIN, glutathione peroxidase, and galectin in the ES of microfilariae (and Mf-containing adult females) compared to the adult males. In addition, searching the ES protein spectra against the Wolbachia database resulted in the identification of 90 Wolbachia-specific proteins, most of which were metabolic enzymes that have not been shown to be immunogenic. This proteomic analysis extends our knowledge of the ES and provides insight into the host–parasite interaction. Human lymphatic filariasis caused by the nematode parasites Brugia malayi and Wuchereria bancrofti are a major cause of concern in tropical countries. Studies over several decades have identified various proteins of these parasites that have highlighted their role in host–parasite interactions and possible chemotherapeutic and prophylactic interventions. The availability of the parasite genome facilitates the identification of all of the proteins of the parasite that could interact with the host. In this study, we have attempted to identify the excretory-secretory proteins of the various stages of the parasite that could be maintained in vitro for a limited period utilizing a high-throughput proteomics approach. We observe and report that the parasites expend resources to secrete out various molecules that they utilize to evade the host immune system and modulate its responses. Further, this study also provides information on the predicted hypothetical proteins to be bonafide proteins and thus a catalogue of the excretory-secretory proteins towards a better understanding of the host–parasite interactions.
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影响因子：
14.9
作者：
Finn RD;Mistry J;Tate J;Coggill P;Heger A;Pollington JE;Gavin OL;Gunasekaran P;Ceric G;Forslund K;Holm L;Sonnhammer EL;Eddy SR;Bateman A
通讯作者：
Bateman A
DOI：
10.1016/0169-4758(95)80207-x
发表时间：
1995-07-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
FUHRMAN, JA
通讯作者：
FUHRMAN, JA
影响因子：
56.9
作者：
Ghedin, Elodie;Wang, Shiliang;Scott, Alan L.
通讯作者：
Scott, Alan L.
DOI：
10.1016/s0035-9203(96)90236-9
发表时间：
1996-05-01
影响因子：
2.2
作者：
Chenthamarakshan, V;Reddy, MVR;Harinath, BC
通讯作者：
Harinath, BC
影响因子：
1.5
作者：
Greenhalgh, CJ;Beckham, SA;Newton, SE
通讯作者：
Newton, SE