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Molecular characterization of Schistosoma mansoni tegument annexins and comparative analysis of antibody responses following parasite infection.
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2019-10-16 , DOI: 10.1016/j.molbiopara.2019.111231
Chiuan Yee Leow 1 , Charlene Willis 2 , Chiuan Herng Leow 3 , Andreas Hofmann 4 , Malcolm Jones 5
Affiliation  

Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca2+. All annexin members evaluated in this study were immunolocalized to the tegument, with immunoreactivity also occurring in cells and in muscle of adult parasites. All four recombinant annexins were immunoreactive and they were recognized by the sera of mice infected with S. mansoni. In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.



中文翻译:

曼氏血吸虫皮膜联蛋白的分子表征和寄生虫感染后抗体反应的比较分析。

血吸虫是寄生性血吸虫,感染了全世界约2.5亿人。这种被称为血吸虫病的疾病是仅次于疟疾的第二大热带寄生虫病。吡喹酮是目前被许可用于血吸虫病的唯一有效药物,并且对该药物的耐药性存在担忧。已经进行了很多努力来开发针对血吸虫病的疫苗,以在流行地区提供长期保护。已经提出与表面相关的蛋白质,尤其是在体壁或外皮中表达的蛋白质,可能成为疫苗的靶标。其中,膜联蛋白被认为对于这种顶膜系统的稳定性至关重要。在这里,我们介绍了四种同源膜联蛋白,即膜联蛋白B30,膜联蛋白B5a,曼氏葡萄球菌。生物信息学分析表明,在这项研究中没有预测任何膜联蛋白的信号肽。进一步的分析表明,所有四个膜联蛋白的每一个都具有由短而可变的N端区域和一个长C端核心组成的一级结构,该核心包含四个同源的膜联蛋白重复序列​​(I-IV),其中包含五个α螺旋。使用定量PCR评估每种膜联蛋白的生命周期表达谱。结果表明,四个同源膜联蛋白各自的总体转录水平在卵期相对较低,但是在尾c(侵袭性血吸虫幼虫)过渡到血吸虫(侵袭后幼虫)后逐渐增加。圆二色性(CD)表明,rAnnexin B30,rAnnexin B5a和rAnnexin 7a被折叠,表示富含α-螺旋的二级结构内容。当rAnnexin B30,rAnnexin B5a和rAnnexin 7a在Ca存在下孵育时,膜结合亲和力增强2+。在这项研究中评估的所有膜联蛋白成员均被免疫定位在外表皮上,免疫反应性也发生在成虫的细胞和肌肉中。所有四个重组膜联蛋白都是免疫反应的,它们被曼氏链球菌感染的小鼠血清所识别。总之,总体结果显示了曼氏沙门氏菌在宿主-寄生虫相互作用中的膜联蛋白B30,膜联蛋白B5a,膜联蛋白B7a和膜联蛋白B5b的分子特征,并强烈暗示该分子可用于疫苗或诊断开发。

更新日期:2019-10-16
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