Spirocerca lupi is a parasitic and carcinogenic nematode of canids distributed in tropical and subtropical regions around the world. The excretion-secretion proteins (PES) of S. lupi have been suggested to play a role in the pathogenesis of its infection. We aimed to identify the PES of different stages of S. lupi and search for proteins that would be useful for diagnostic, therapeutic and vaccination purposes as well as understand their functions. A nano-UPLC mass spectrometry de novo analysis was performed on proteins collected from cultures of S. lupi L3 larvae, L4 females, adult females and adult males from naturally infected hosts. A total of 211 proteins were identified in all cultures. Accordingly, 117, 130, 99 and 116 proteins were detected in L3 larva, L4 females, adult females and adult males, respectively, with a strong correlation in the biological replicates (Pearson coefficients > 0.73). Fourty-four proteins were detected in all developmental stages, 64 were stage-specific and 49 were exclusively identified in L4 females. Cell compartment enrichment analysis revealed that proteins common to all stages were cytoplasmatic (p < 9.x10-6), whereas L4 unique proteins were in collagen trimers, and macromolecular complexes (p < 0.00001). Functional enrichment analysis of proteins showed significant enrichment in lipid metabolism in L3-unique proteins (p<0.00005), in mannose metabolism and protein de-glycosylation for L4-unique proteins (p < 0.00004), and in phosphorus metabolism in proteins shared by all stages (p <  2.1 x10-9). Interestingly, annexin 6, associated with cancer in humans, was detected in all life stages, but in a larger abundance in L4 females and adults. These findings indicate that S. lupi establishes complex interactions with its hosts by an arsenal of proteins expressed in different patterns in each life stage which influence the pathogenesis and oncogenesis of S. lupi and may be used as potential targets for diagnostic assays, drug targets or vaccine candidates.

中文翻译：

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致癌蠕虫Spirocerca lupi的Secretome揭示了与其不同生命阶段相关的特定寄生虫蛋白。

Spirocerca lupi是一种犬科寄生虫和致癌线虫，分布于世界各地的热带和亚热带地区。有人建议S. lupi的排泄分泌蛋白（PES）在其感染的发病机理中起作用。我们旨在鉴定猪链球菌不同阶段的PES，并寻找可用于诊断，治疗和疫苗接种目的的蛋白质，并了解其功能。对从自然感染宿主的S. lupi L3幼虫，L4雌性，成年雌性和成年雄性培养物中收集的蛋白质进行了纳米UPLC质谱从头分析。在所有培养物中共鉴定出211种蛋白质。因此，分别在L3幼虫，L4雌性，成年雌性和成年雄性中检测到117、130、99和116个蛋白，与生物学重复具有很强的相关性（皮尔森系数> 0.73）。在所有发育阶段共检测到44种蛋白质，其中64种具有阶段特异性，而在L4雌性中仅鉴定出49种。细胞室富集分析显示，所有阶段共有的蛋白质是细胞质的（p <9.x10-6），而L4独特的蛋白质存在于胶原三聚体和大分子复合物中（p <0.00001）。蛋白质的功能富集分析显示，L3独特蛋白中的脂类代谢显着富集（p <0.00005），L4独特蛋白中的甘露糖代谢和蛋白去糖基化（p <0.00004），以及所有人共享蛋白中的磷代谢阶段（p <2.1 x10-9）。有趣的是，在所有生命阶段都发现了与人类癌症相关的膜联蛋白6，但在L4的女性和成年人中，数量较多。这些发现表明，卢氏链球菌通过在每个生命阶段以不同模式表达的蛋白质库与宿主建立复杂的相互作用，这会影响卢氏链球菌的发病机理和致癌作用，并且可以用作诊断测定，药物靶标或候选疫苗。