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感染人体时,猪蛔虫假定的毒力相关基因的表达。

Expression of Ascaris lumbricoides putative virulence-associated genes when infecting a human host.

机构信息

Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia.

出版信息

Parasit Vectors. 2021 Mar 23;14(1):176. doi: 10.1186/s13071-021-04680-y.

Abstract

BACKGROUND

Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. It is suggested that helminths are capable of evading and manipulating the host immune system through the release of a spectrum of worm proteins which underpins their long-term survival in the host. We hypothesise that the worm overexpresses these proteins when infecting adults compared to children to cirvumvent the more robust defence mechanisms of adults. However, little is known about the parasite's genes and encoded proteins involved during A. lumbricoides infection. Hence, this study was conducted to assess the expression profile of putative virulence-associated genes during an active infection of adults and children.

METHODS

In this study, quantitative PCR was performed to evaluate the expression profile of putative virulence-associated genes in A. lumbricoides isolated from infected children and adults. The study was initiated by collecting adult worms expelled from adults and children following anthelminthic treatment. High-quality RNA was successfully extracted from each of six adult worms expelled by three adults and three children, respectively. Eleven putative homologues of helminth virulence-associated genes reported in previous studies were selected, primers were designed and specific amplicons of A. lumbricoides genes were noted. The expression profiles of these putative virulence-associated genes in A. lumbricoides from infected adults were compared to those in A. lumbricoides from infected children.

RESULTS

The putative virulence-associated genes VENOM, CADHERIN and PEBP were significantly upregulated at 166-fold, 13-fold and fivefold, respectively, in adults compared to children. Conversely, the transcription of ABA-1 (fourfold), CATH-L (threefold) and INTEGRIN (twofold) was significantly suppressed in A. lumbricoides from infected adults.

CONCLUSIONS

On the basis of the expression profile of the putative virulence-associated genes, we propose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions.

摘要

背景

蛔虫是全世界最常见的土壤传播性蠕虫感染病原体,估计有全球 4.5 亿人感染这种线虫。有研究表明,蠕虫通过释放一系列支持其在宿主体内存活的蠕虫蛋白,从而逃避和操纵宿主免疫系统。我们假设,蠕虫在感染成年人时会过度表达这些蛋白质,以规避成年人更强的防御机制。然而,人们对寄生虫在感染过程中涉及的基因和编码蛋白知之甚少。因此,本研究旨在评估成人和儿童活动性感染期间潜在的与毒力相关基因的表达谱。

方法

在这项研究中,通过定量 PCR 评估从感染儿童和成人中分离的蛔虫潜在的与毒力相关基因的表达谱。该研究通过收集驱虫治疗后从成年人和儿童中排出的成虫开始。成功地从三个成年人和三个儿童分别排出的六条成虫中提取了高质量的 RNA。选择了先前研究中报道的 11 种潜在的蠕虫毒力相关基因的同源物,设计了引物,并注意到了蛔虫基因的特异性扩增子。将感染成年人的蛔虫中这些潜在的与毒力相关基因的表达谱与感染儿童的蛔虫进行了比较。

结果

与儿童相比,VENOM、CADHERIN 和 PEBP 等潜在的与毒力相关基因在成虫中分别显著上调了 166 倍、13 倍和 5 倍。相反,ABA-1(4 倍)、CATH-L(3 倍)和 INTEGRIN(2 倍)的转录在感染成年人的蛔虫中显著受到抑制。

结论

根据潜在的与毒力相关基因的表达谱,我们提出这些编码蛋白在逃避机制中可能具有潜在作用,这可能有助于开发治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a408/7989106/80559217a5d2/13071_2021_4680_Fig1_HTML.jpg

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