On the importance of targeting parasite stem cells in anti-echinococcosis drug development.
On the importance of targeting parasite stem cells in anti-echinococcosis drug development.
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DOI：
10.1051/parasite/2014070
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Koziol U
中科院分区：
文献类型：
--
作者：
Brehm K;Koziol U
泡状和囊状棘球蚴病是一种危及生命的疾病，由多房棘球绦虫和棘球绦虫的幼虫引起。granulosus。在这两种情况下，中间宿主，如人类，通过口服六钩蚴幼虫感染，随后是无性繁殖和后绦虫在宿主器官内几乎不受限制的生长。除了手术，包虫病的治疗依赖于苯并咪唑为基础的化疗，针对寄生虫β-微管蛋白。然而，由于β-微管蛋白在绦虫和人类之间高度相似，苯并咪唑只能以寄生虫抑制剂量应用，并且与不良副作用相关。主要是为了寻找替代药物靶点，E。multilocularis和E.最近已经对颗粒绦虫进行了表征，揭示了大量由后绦虫表达的可药用靶标。此外，最近的细胞生物学研究表明，E。多室细胞采用多能干细胞，称为萌发细胞，这是唯一能够增殖并产生所有分化细胞的寄生虫细胞。因此，萌发细胞是介导大肠杆菌增殖的关键细胞类型。多室的E.在宿主器官内的颗粒体，并且也应该负责在停止化疗后的寄生虫复发。有趣的是，最近的研究还表明，萌发细胞可能对化疗不太敏感，因为它们表达对苯并咪唑具有有限亲和力的β-微管蛋白同种型。在这篇文章中，我们简要地回顾了最近的研究结果有关棘球蚴基因组学和干细胞的研究，并提出未来的研究抗棘球蚴病的药物也应该集中在寄生虫的干细胞群体。
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.
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影响因子：
3.8
作者：
Schubert A;Koziol U;Cailliau K;Vanderstraete M;Dissous C;Brehm K
通讯作者：
Brehm K
影响因子：
5.4
作者：
Hemer S;Konrad C;Spiliotis M;Koziol U;Schaack D;Förster S;Gelmedin V;Stadelmann B;Dandekar T;Hemphill A;Brehm K
通讯作者：
Brehm K
影响因子：
9.6
作者：
Skinner DE;Rinaldi G;Koziol U;Brehm K;Brindley PJ
通讯作者：
Brindley PJ
影响因子：
4
作者：
Konrad, C;Kroner, A;Brehm, K
通讯作者：
Brehm, K
影响因子：
5.8
作者：
Gelmedin, Verena;Caballero-Gamiz, Rocio;Brehm, Klaus
通讯作者：
Brehm, Klaus