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广东血管圆线虫人体病原体的初步分子特征。

Preliminary molecular characterization of the human pathogen Angiostrongylus cantonensis.

机构信息

Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan, 2nd Road, Guangzhou, 510080, PR China.

出版信息

BMC Mol Biol. 2009 Oct 25;10:97. doi: 10.1186/1471-2199-10-97.

Abstract

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 approximately 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.

摘要

背景

食源性食源性公共卫生问题日益严重,全球范围内的病例数量不断增加,尤其是在中国内地。引起这种严重疾病的病原体是广州管圆线虫。然而,人们对广州管圆线虫的遗传学和基础生物学知之甚少。

结果

构建了广州管圆线虫第四期幼虫 cDNA 文库,测序了大约 1200 个克隆。生物信息学分析揭示了 378 个 cDNA 簇,其中 54.2%在 cutoff expectation 值为 10(-20)的情况下与已知基因匹配。在这 378 个独特的 cDNA 中,有 168 个含有开放阅读框,编码含有平均 238 个氨基酸的蛋白质。通过 Gene Ontology 分析对这些编码蛋白的功能进行特征描述,发现富含具有结合和催化活性的蛋白。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。使用酶联免疫吸附试验和组织病理学检查测试了四种蛋白质的免疫原性。虽然敏感性相对较低,但四种蛋白质中的每一种的特异性都优于幼虫的粗体和排泄/分泌抗原。我们进一步表明,用重组半胱氨酸蛋白酶抑制剂免疫的小鼠对广州管圆线虫感染有部分保护作用,该抑制剂是四个 cDNA 候选基因之一的产物。

结论

本研究提供的大量数据大大扩展了有关人类病原体广州管圆线虫的遗传信息,应成为血管圆线虫研究人员的重要资源。因此,这项工作为诊断和控制人类血管圆线虫病的分子方法提供了一个起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6766/2774698/191c919ba414/1471-2199-10-97-1.jpg

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