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曼氏血吸虫幼虫感染哺乳动物宿主相关的基因表达模式。

Gene expression patterns in larval Schistosoma mansoni associated with infection of the mammalian host.

机构信息

University of York, Heslington, United Kingdom.

出版信息

PLoS Negl Trop Dis. 2011 Aug;5(8):e1274. doi: 10.1371/journal.pntd.0001274. Epub 2011 Aug 30.

Abstract

BACKGROUND

The infective schistosome cercaria develops within the intramolluscan daughter sporocyst from an undifferentiated germ ball, during which synthesis of proteins essential for infection occurs. When the aquatic cercaria locates the mammalian host it rapidly penetrates into the epidermis using glandular secretions. It then undergoes metamorphosis into the schistosomulum, including replacement of its tegument surface membranes, a process taking several days before it exits the skin. Patterns of gene expression underlying this transition have been characterised.

METHODS AND PRINCIPAL FINDINGS

All gene models from the S. mansoni genome (www.GeneDB.org) were incorporated into a high-density oligonucleotide array. Double-stranded cDNA from germ balls, cercariae, and day 3 schistosomula was hybridised to the array without amplification. Statistical analysis was performed using Bioconductor to reveal differentially transcribed loci. Genes were categorised on the basis of biological process, tissue association or molecular function to aid understanding of the complex processes occurring. Genes necessary for DNA replication were enriched only in the germ ball, while those involved in translation were up-regulated in the germ ball and/or day 3 schistosomulum. Different sets of developmental genes were up-regulated at each stage. A large number of genes encoding elastases and invadolysins, and some venom allergen-like proteins were up-regulated in the germ ball, those encoding cysteine and aspartic proteases in the cercaria and schistosomulum. Micro exon genes encoding variant secreted proteins were highly up-regulated in the schistosomulum along with tegument and gut-associated genes, coincident with remodelling of the parasite body. Genes encoding membrane proteins were prominently up-regulated in the cercaria and/or day 3 schistosomulum.

CONCLUSIONS/SIGNIFICANCE: Our study highlights an expanded number of transcripts encoding proteins potentially involved in skin invasion. It illuminates the process of metamorphosis into the schistosomulum and highlights the very early activation of gut-associated genes whilst revealing little change in the parasite's energy metabolism or stress responses.

摘要

背景

感染性血吸虫尾蚴在软体动物内部的子孢子中发育,由未分化的胚球形成,在此过程中合成感染所需的必需蛋白。当水生尾蚴找到哺乳动物宿主时,它会利用腺分泌迅速穿透表皮。然后,它会经历到童虫的变态,包括替换其表皮表面膜,这个过程需要几天时间,然后它才会离开皮肤。已经描述了这种转变所涉及的基因表达模式。

方法和主要发现

从 S. mansoni 基因组(www.GeneDB.org)中所有的基因模型都被纳入高密度寡核苷酸阵列中。未经扩增,从胚球、尾蚴和第 3 天的童虫中提取双链 cDNA 并与微阵列杂交。使用 Bioconductor 进行统计分析,以揭示差异转录的基因座。根据生物过程、组织关联或分子功能对基因进行分类,以帮助理解发生的复杂过程。仅在胚球中富集了用于 DNA 复制的基因,而参与翻译的基因在胚球和/或第 3 天的童虫中上调。在每个阶段都上调了不同的发育基因集。大量编码弹性蛋白酶和侵袭素的基因,以及一些毒液过敏原样蛋白在胚球中上调,在尾蚴和童虫中编码半胱氨酸和天冬氨酸蛋白酶的基因上调。编码变体分泌蛋白的微外显子基因在童虫中高度上调,与体壁和肠道相关基因一起,与寄生虫体的重塑同时发生。编码膜蛋白的基因在尾蚴和/或第 3 天的童虫中显著上调。

结论/意义:我们的研究突出了大量潜在参与皮肤入侵的蛋白质编码转录本。它阐明了向童虫变态的过程,并突出了肠道相关基因的早期激活,同时揭示了寄生虫的能量代谢或应激反应几乎没有变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f7/3166049/781d018a830a/pntd.0001274.g001.jpg

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