Brehm Klaus, Koziol Uriel
Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany - Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Parasite. 2014;21:72. doi: 10.1051/parasite/2014070. Epub 2014 Dec 22.
The life-threatening diseases alveolar and cystic echinococcoses are caused by larvae of the tapeworms Echinococcus multilocularis and E. granulosus, respectively. In both cases, intermediate hosts, such as humans, are infected by oral uptake of oncosphere larvae, followed by asexual multiplication and almost unrestricted growth of the metacestode within host organs. Besides surgery, echinococcosis treatment relies on benzimidazole-based chemotherapy, directed against parasite beta-tubulin. However, since beta-tubulins are highly similar between cestodes and humans, benzimidazoles can only be applied at parasitostatic doses and are associated with adverse side effects. Mostly aiming at identifying alternative drug targets, the nuclear genome sequences of E. multilocularis and E. granulosus have recently been characterized, revealing a large number of druggable targets that are expressed by the metacestode. Furthermore, recent cell biological investigations have demonstrated that E. multilocularis employs pluripotent stem cells, called germinative cells, which are the only parasite cells capable of proliferation and which give rise to all differentiated cells. Hence, the germinative cells are the crucial cell type mediating proliferation of E. multilocularis, and most likely also E. granulosus, within host organs and should also be responsible for parasite recurrence upon discontinuation of chemotherapy. Interestingly, recent investigations have also indicated that germinative cells might be less sensitive to chemotherapy because they express a beta-tubulin isoform with limited affinity to benzimidazoles. In this article, we briefly review the recent findings concerning Echinococcus genomics and stem cell research and propose that future research into anti-echinococcosis drugs should also focus on the parasite's stem cell population.
危及生命的疾病肺泡型和囊型棘球蚴病分别由绦虫多房棘球绦虫和细粒棘球绦虫的幼虫引起。在这两种情况下，中间宿主（如人类）通过经口摄取六钩蚴幼虫而被感染，随后在宿主机官内进行无性繁殖且原头蚴几乎不受限制地生长。除了手术，棘球蚴病的治疗依赖于针对寄生虫β-微管蛋白的基于苯并咪唑的化疗。然而，由于绦虫和人类的β-微管蛋白高度相似，苯并咪唑只能以抑制寄生虫生长的剂量使用，且会产生不良副作用。最近对多房棘球绦虫和细粒棘球绦虫的核基因组序列进行了表征，主要目的是确定替代药物靶点，结果揭示了大量由原头蚴表达的可成药靶点。此外，最近的细胞生物学研究表明，多房棘球绦虫利用多能干细胞，即生发细胞，这是唯一能够增殖的寄生虫细胞，可产生所有分化细胞。因此，生发细胞是介导多房棘球绦虫（很可能还有细粒棘球绦虫）在宿主机官内增殖的关键细胞类型，也应该是化疗停止后寄生虫复发的原因。有趣的是，最近的研究还表明，生发细胞可能对化疗不太敏感，因为它们表达一种对苯并咪唑亲和力有限的β-微管蛋白亚型。在本文中，我们简要回顾了关于棘球绦虫基因组学和干细胞研究的最新发现，并提出未来抗棘球蚴病药物的研究也应关注寄生虫的干细胞群体。
