The role of sialyl glycan recognition in host tissue tropism of the avian parasite Eimeria tenella.
The role of sialyl glycan recognition in host tissue tropism of the avian parasite Eimeria tenella.
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DOI：
10.1371/journal.ppat.1002296
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发表时间：
2011-10
期刊：
影响因子：
6.7
通讯作者：
Matthews S
中科院分区：
文献类型：
--
作者：
Lai L;Bumstead J;Liu Y;Garnett J;Campanero-Rhodes MA;Blake DP;Palma AS;Chai W;Ferguson DJ;Simpson P;Feizi T;Tomley FM;Matthews S
艾美耳球虫属是一组非常成功的细胞内原生动物寄生虫，在家禽的肠上皮细胞内发育，引起球虫病。由于抗球虫药物的耐药性和制造活疫苗的费用，有必要更深入地了解艾美球虫与其宿主的关系，以期开发重组疫苗。艾美球虫拥有微线体凝集素 (MIC) 家族，其中含有微线体粘附重复区域 (MARR)。我们发现柔嫩艾美耳球虫的主要 MARR 蛋白 EtMIC3 在入侵的早期阶段就部署在寄生虫-宿主界面上。 EtMIC3 由七个串联的 MAR1 型结构域组成，其对唾液酸化聚糖具有高度特异性，如基于细胞的测定和碳水化合物微阵列分析所示。在鸡盲肠上皮中观察到的 EtMIC3 的受限组织染色模式表明，EtMIC3 有助于引导寄生虫到达鸡肠道中的入侵部位。微阵列分析还揭示了 EtMIC3 缺乏对以唾液酸 N-乙醇酰形式终止的聚糖序列的识别。因此，该寄生虫很好地适应了缺乏N-乙醇酰神经氨酸的鸟类宿主。我们提供了对 MAR1 结构域家族的新结构见解，并揭示了基于唾液酸的碳水化合物识别的原子分辨率基础。最后，初步的鸡免疫试验提供了证据，表明重组 EtMIC3 蛋白和 EtMIC3 DNA 是有效的候选疫苗。 艾美耳球虫属是鸟类肠道中非常成功的原生动物寄生虫，也是现代家禽养殖中最重要的疾病之一。经济影响巨大，导致该行业损失数十亿美元，因此迫切需要新的治疗方法。抗球虫药物因耐药性而受到阻碍，活疫苗的制造成本昂贵，并且很少有重组疫苗抗原被详细表征。我们发现，来自柔嫩艾美耳球虫的微线体蛋白 MIC3 在入侵的早期阶段就部署在寄生虫与宿主的界面上。我们提供了新的原子分辨率见解，以了解其对携带唾液酸的聚糖的偏好，并证明了其在侵袭中的作用。我们还提供证据表明基于 EtMIC3 的疫苗在初步免疫研究中可产生保护作用。
Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates. Eimeria spp. are highly successful protozoan parasites of the intestine of birds and one of the most important diseases in modern poultry farming. The economic impact is significant causing billion dollar losses to the industry and as a result there is pressing need for new therapeutic approaches. Anticoccidial drugs are thwarted by resistance, live vaccines are expensive to manufacture and few recombinant vaccine antigens have been characterized in detail. We show that the microneme protein, MIC3 from Eimeria tenella, is deployed at the parasite-host interface during the early stages of invasion. We provide new atomic resolution insight into its predilection for sialic acid-bearing glycans and demonstrate its role in invasion. We also provide evidence that EtMIC3-based vaccines induce protection in preliminary immunization studies.
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影响因子：
3.4
作者：
Lal, Kalpana;Bromley, Elizabeth;Oakes, Richard;Prieto, Judith Helena;Sanderson, Sanya J.;Kurian, Dominic;Hunt, Lawrence;Yates, John R., III;Wastling, Jonathan M.;Sinden, Robert E.;Tomley, Fiona M.
通讯作者：
Tomley, Fiona M.
影响因子：
1.5
作者：
Labbé, M;de Venevelles, P;Péry, P
通讯作者：
Péry, P
影响因子：
4
作者：
Jung, C;Lee, CYF;Grigg, ME
通讯作者：
Grigg, ME
6-Sulfo siallyl Lewis X是陆地家禽H5，H6，H7和H9流感病毒所识别的常见受体决定因素。
影响因子：
4.8
作者：
Gambaryan AS;Tuzikov AB;Pazynina GV;Desheva JA;Bovin NV;Matrosovich MN;Klimov AI
通讯作者：
Klimov AI
微生物蛋白在弓形虫贡献毒力中的协同作用。
影响因子：
15.3
作者：
Céréde, O;Dubremetz, JF;Soête, M;Deslée, D;Vial, H;Bout, D;Lebrun, M
通讯作者：
Lebrun, M