Comprehensive developmental somatic proteome atlas of Haemonchus contortus underpinned by a chromosome-scale genome and deep tandem mass spectrometry.

IF 3.5 2区 医学 Q1 PARASITOLOGY
Tao Wang, Yuanting Zheng, Neil D Young, Ching-Seng Ang, Robin B Gasser
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Abstract

Background: Haemonchus contortus is a highly pathogenic, blood-feeding nematode that causes widespread disease and significant economic loss in livestock worldwide. Previous proteomic studies were constrained by incomplete genomic resources and limited analytical sensitivity, impeding comprehensive profiling across life stages.

Methods: In this study, we integrated advanced tandem mass spectrometry with a chromosome-scale genome assembly of the Haecon-5 strain to construct the most detailed somatic proteome of H. contortus to date.

Results: We identified and quantified 7002 proteins across five key developmental stages/sexes-i.e. eggs, third-stage larvae (L3s), fourth-stage larvae (L4s), and adult female (Af) and adult male (Am) worms-tripling the number identified in an earlier study. Comparative analyses revealed pronounced stage-specific expression and functional specialisation, with parasitic stages enriched in proteins linked to metabolism, cellular function and environmental sensing. Fifteen proteins associated with the hypoxia-inducible factor 1 (HIF-1) signalling pathway were upregulated in parasitic stages, suggesting a role in adaptation to hypoxia. Additionally, 150 proteases implicated in haemoglobin degradation were characterised, and functional assays confirmed markedly elevated haemoglobinolytic activity in blood-feeding stages.

Conclusions: These findings offer key insights into H. contortus development and parasitism, and establish a high-resolution proteomic framework to underpin fundamental biological studies and to enable the discovery of molecular targets for novel interventions against this and related nematodes.

Abstract Image

Abstract Image

Abstract Image

由染色体尺度基因组和深度串联质谱技术支持的弯曲血蜱发育体细胞蛋白质组图谱。
背景:弯曲血蜱是一种高致病性的血食性线虫,在世界范围内引起广泛的疾病和重大的牲畜经济损失。先前的蛋白质组学研究受到不完整的基因组资源和有限的分析灵敏度的限制,阻碍了跨生命阶段的全面分析。方法:将先进的串联质谱技术与Haecon-5菌株的染色体尺度基因组组装相结合,构建了迄今为止最详细的H. contortus体细胞蛋白质组。结果:我们在5个关键发育阶段/性别中鉴定并量化了7002个蛋白质。卵、第三期幼虫(L3s)、第四期幼虫(L4s)、成年雌虫(Af)和成年雄虫(Am)——数量是先前研究中发现的三倍。比较分析揭示了明显的阶段特异性表达和功能特化,寄生阶段富含与代谢、细胞功能和环境感知相关的蛋白质。15种与缺氧诱导因子1 (HIF-1)信号通路相关的蛋白在寄生期被上调,这表明它们在适应缺氧中起作用。此外,150个与血红蛋白降解有关的蛋白酶被表征,功能测定证实在血液喂养阶段血红蛋白溶解活性显著升高。结论:这些发现为线虫的发育和寄生提供了重要的见解,并建立了一个高分辨率的蛋白质组学框架,为基础生物学研究提供了基础,并为针对线虫和相关线虫的新干预措施发现了分子靶点。
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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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