Müller Joachim, Zumkehr Beatrice, Heller Manfred, Uldry Anne-Christine, Braga-Lagache Sophie, Lundström-Stadelmann Britta
Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Proteomics and Mass Spectrometry Core Facility (PMSCF), Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
Int J Mol Sci. 2025 Apr 1;26(7):3266. doi: 10.3390/ijms26073266.
Metacestodes of are the causative agents of alveolar echinococcosis, a neglected, life-threatening, zoonotic disease. To study these metacestodes in vitro, a model system using a culture medium conditioned by rat hepatoma cells is available. A key question is how the parasite interacts with the host and, in particular, which host-derived compounds are taken up. In this study, we focus on the uptake of host-derived proteins. Studies with artificially labeled proteins suggest that this uptake may occur independently of protein size or charge. Closer investigation using proteomics draws, however, a different picture. Of 1170 host (i.e., rat or bovine) proteins as identified by LC-MS/MS-based proteomics present in the culture medium, only 225 are found in metacestode vesicle tissue or fluid. Moreover, their relative abundances differ. Serum albumin, the most abundant culture medium host protein, is only the third most abundant protein in vesicle fluid, where Alpha-2-HS-glycoprotein becomes the most abundant protein. In vesicle fluid obtained ex vivo from experimentally infected mice, the situation is again different, with histone isoforms as the most abundant proteins. This suggests that while maintaining their internal milieu constant, metacestodes may adjust the spectrum of host proteins taken up. Potential uptake mechanisms and functions are discussed.
多房棘球绦虫的中绦期幼虫是泡型包虫病的病原体,这是一种被忽视的、危及生命的人畜共患病。为了在体外研究这些中绦期幼虫,有一种使用经大鼠肝癌细胞条件培养的培养基的模型系统。一个关键问题是寄生虫如何与宿主相互作用,特别是摄取哪些宿主来源的化合物。在本研究中,我们聚焦于宿主来源蛋白质的摄取。对人工标记蛋白质的研究表明,这种摄取可能与蛋白质的大小或电荷无关。然而,使用蛋白质组学进行的进一步研究呈现出不同的情况。在基于液相色谱-串联质谱的蛋白质组学鉴定出的培养基中存在的1170种宿主(即大鼠或牛)蛋白质中,只有225种在中绦期幼虫囊泡组织或囊液中被发现。此外,它们的相对丰度也不同。血清白蛋白是培养基中最丰富的宿主蛋白质,但在囊液中仅是第三丰富的蛋白质,而α-2-HS-糖蛋白成为最丰富的蛋白质。在从实验感染小鼠体内获取的离体囊液中,情况又有所不同,组蛋白异构体是最丰富的蛋白质。这表明,中绦期幼虫在维持其内部环境恒定的同时,可能会调整所摄取的宿主蛋白质谱。文中还讨论了潜在的摄取机制和功能。