PDF(Pubmed)
Abstract：
The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm\'s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm Necator americanus identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male A. ceylanicum. The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential.
摘要：
哺乳动物宿主中钩虫感染建立和维持的动态宿主-寄生虫机制仍然知之甚少，但主要由钩虫的排泄/分泌产物（ESPs）介导。具有广泛的生物学功能。我们使用超高效质谱法全面分析和比较了人畜共患钩虫Ancylostomaceylanicum的女性和男性ESPs，它是狗的天然寄生虫，猫,和人类。我们改进了基因组注释，将蛋白质编码基因的数量减少了49％，同时将完整性从92％提高到96％。与以前的基因组注释相比，我们在女性和男性ESP中检测到11%和10%以上的光谱，分别,使用这个改进的版本，确定总共795个ESPs(男女70%，与其余的性别特定)。使用功能数据库(KEGG，GO和Interpro)，确定了常见和特定性别的丰富功能。与专门感染人类的钩虫Necatoramericanus进行比较，确定了物种特异性和保守性的ESPs。这是鉴定来自雌性和雄性西兰曲霉的ESPs的第一项研究。这些发现提供了对钩虫蛋白功能的更深入了解，以确保宿主的长期生存，并促进转基因钩虫的未来工程和介导ESPs高水平表达的调节元件的分析。此外，研究结果扩大了潜在疫苗和诊断靶点的列表,并确定了可用于抗炎潜力的生物制剂.
