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Preliminary molecular characterization of the human pathogen Angiostrongylus cantonensis

机译:人类病原体广州广州圆线虫的初步分子表征

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Background Human angiostrongyliasis is an emerging food-borne public health problem, with the number of cases increasing worldwide, especially in mainland China. Angiostrongylus cantonensis is the causative agent of this severe disease. However, little is known about the genetics and basic biology of A. cantonensis.Results A cDNA library of A. cantonensis fourth-stage larvae was constructed, and ~1,200 clones were sequenced. Bioinformatic analyses revealed 378 cDNA clusters, 54.2% of which matched known genes at a cutoff expectation value of 10~(-20). Of these 378 unique cDNAs, 168 contained open reading frames encoding proteins containing an average of 238 amino acids. Characterization of the functions of these encoded proteins by Gene Ontology analysis showed enrichment in proteins with binding and catalytic activity. The observed pattern of enzymes involved in protein metabolism, lipid metabolism and glycolysis may reflect the central nervous system habitat of this pathogen. Four proteins were tested for their immunogenicity using enzyme-linked immunosorbent assays and histopathological examinations. The specificity of each of the four proteins was superior to that of crude somatic and excretory/secretory antigens of larvae, although their sensitivity was relatively low. We further showed that mice immunized with recombinant cystatin, a product of one of the four cDNA candidate genes, were partially protected from A. cantonensis infection.Conclusion The data presented here substantially expand the available genetic information about the human pathogen A. cantonensis, and should be a significant resource for angiostrongyliasis researchers. As such, this work serves as a starting point for molecular approaches for diagnosing and controlling human angiostrongyliasis.
机译:背景技术人类血管紧闭症是一个新兴的食源性公共卫生问题,在世界范围内,特别是在中国大陆,病例数正在增加。广东圆管圆线虫是这种严重疾病的病原体。结果对广州农杆菌的遗传学和基础生物学知之甚少。结果构建了广州农杆菌第四阶段幼虫的cDNA文库,并测序了约1200个克隆。生物信息学分析揭示了378个cDNA簇,其中54.2%与已知基因匹配,其预期截止值为10〜(-20)。在这378个独特的cDNA中,有168个包含开放阅读框,这些阅读框编码平均包含238个氨基酸的蛋白质。通过基因本体分析对这些编码蛋白的功能进行了表征,结果表明该蛋白富含结合和催化活性。观察到的参与蛋白质代谢,脂质代谢和糖酵解的酶的模式可能反映了该病原体的中枢神经系统栖息地。使用酶联免疫吸附测定和组织病理学检查测试了四种蛋白质的免疫原性。四种蛋白质中每种蛋白质的特异性都优于幼虫的粗体细胞和排泄/分泌抗原,尽管它们的敏感性相对较低。我们进一步表明,用重组胱抑素(这四个cDNA候选基因之一的产物)免疫的小鼠受到了部分广州曲霉感染的保护。结论本文提供的数据大大扩展了有关人类病原体广州曲霉的可用遗传信息。对于血管平滑肌病研究人员而言,应该是重要的资源。因此,这项工作为诊断和控制人血管平滑肌病的分子方法提供了起点。

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