Maizels R M, Tetteh K K, Loukas A
Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh, UK.
Int J Parasitol. 2000 Apr 10;30(4):495-508. doi: 10.1016/s0020-7519(00)00022-9.
Toxocara canis is a widely distributed nematode parasite which reaches maturity in dogs. However, eggs voided by canid animals are infective to a very wide range of paratenic hosts including humans. In noncanid hosts, infective larvae emerge from the eggs and invade the soft tissues, often entering the brain and musculature. Such larvae may remain for many months or years in these tissues without further growth or differentiation, and yet appear to evade inflammatory reactions or other modes of immune attack. To understand the ability of T. canis larvae to survive in the immunocompetent host, we have undertaken a molecular analysis of the major genes expressed at this stage. By a combination of protein sequencing, gene identification, and expressed sequence tag (EST) analysis we have characterised a range of potentially important gene products from this parasite. Some of these are homologues of prominent mammalian proteins such as C-type lectins (represented by the secreted products TES-32 and TES-70), and mucins (TES-120), and additional products show strong similarities to known cysteine proteases, phosphatidylethanolamine-binding proteins and other ligands. A number of these proteins include a conspicuous 36-amino acid motif containing six cysteines. This domain (termed NC6 or SXC) appears to be an evolutionarily mobile module, which in T. canis is combined with a spectrum of diverse functional domains in different genes. In addition, we have identified a set of novel gene sequences that show no resemblance to any genes encoded by the free-living nematode C. elegans. Four of these are designated abundant novel transcripts, and collectively these account for nearly 20% of the cDNA isolated from the arrested infective stage. Such parasite-specific genes expressed at a high level by a stage that shows remarkable endurance may represent critical products necessary for the success of the parasitic mode of life.
犬弓首线虫是一种广泛分布的线虫寄生虫,在犬类体内发育成熟。然而,犬科动物排出的虫卵对包括人类在内的多种转续宿主具有感染性。在非犬科宿主中,感染性幼虫从虫卵中孵出并侵入软组织,常进入大脑和肌肉组织。这些幼虫可在这些组织中停留数月或数年,不再进一步生长或分化,但似乎能逃避炎症反应或其他免疫攻击方式。为了解犬弓首线虫幼虫在免疫功能正常的宿主体内存活的能力,我们对该阶段表达的主要基因进行了分子分析。通过蛋白质测序、基因鉴定和表达序列标签(EST)分析相结合的方法,我们对该寄生虫一系列潜在重要的基因产物进行了表征。其中一些是与重要哺乳动物蛋白同源的蛋白,如C型凝集素(以分泌产物TES-32和TES-70为代表)和粘蛋白(TES-120),其他产物与已知的半胱氨酸蛋白酶、磷脂酰乙醇胺结合蛋白和其他配体有很强的相似性。这些蛋白质中有许多包含一个由六个半胱氨酸组成的明显的36个氨基酸基序。这个结构域(称为NC6或SXC)似乎是一个在进化中可移动的模块,在犬弓首线虫中,它与不同基因中的一系列不同功能结构域结合。此外,我们还鉴定出一组新的基因序列,它们与自由生活线虫秀丽隐杆线虫编码的任何基因都没有相似之处。其中四个被指定为丰富的新转录本,这些转录本总共占从静止感染阶段分离的cDNA的近20%。在一个表现出显著耐受性的阶段高水平表达的此类寄生虫特异性基因可能代表了寄生生活方式成功所必需的关键产物。