title: Recent advances in Echinococcus genomics and stem cell research.
abstract: Alveolar and cystic echinococcosis, caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively, are life-threatening diseases and very difficult to treat. The introduction of benzimidazole-based chemotherapy, which targets parasite β-tubulin, has significantly improved the life-span and prognosis of echinococcosis patients. However, benzimidazoles show only parasitostatic activity, are associated with serious adverse side effects and have to be administered for very long time periods, underlining the need for new drugs. Very recently, the nuclear genomes of E. multilocularis and E. granulosus have been characterised, revealing a plethora of data for gaining a deeper understanding of host-parasite interaction, parasite development and parasite evolution. Combined with extensive transcriptome analyses of Echinococcus life cycle stages these investigations also yielded novel clues for targeted drug design. Recent years also witnessed significant advancements in the molecular and cellular characterisation of the Echinococcus 'germinative cell' population, which forms a unique stem cell system that differs from stem cells of other organisms in the expression of several genes associated with the maintenance of pluripotency. As the only parasite cell type capable of undergoing mitosis, the germinative cells are central to all developmental transitions of Echinococcus within the host and to parasite expansion via asexual proliferation. In the present article, we will briefly introduce and discuss recent advances in Echinococcus genomics and stem cell research in the context of drug design and development. Interestingly, it turns out that benzimidazoles seem to have very limited effects on Echinococcus germinative cells, which could explain the high recurrence rates observed after chemotherapeutic treatment of echinococcosis patients. This clearly indicates that future efforts into the development of parasitocidal drugs should also target the parasite's stem cell system.
authors: University of Würzburg, Institute of Hygiene and Microbiology, Würzburg, Germany; Sección Bioquímica, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay.
authors: U
authors: U
authors: Koziol
authors: University of Würzburg, Institute of Hygiene and Microbiology, Würzburg, Germany. Electronic address: kbrehm@hygiene.uni-wuerzburg.de.
authors: K
authors: K
authors: Brehm
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000592:standards / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D015195:Drug Design; D004443:Echinococcosis / Q000188:drug therapy / Q000469:parasitology*; D004446:Echinococcus / Q000235:genetics*; D049751:Genome, Helminth; D023281:Genomics / Q000639:trends*; D057905:Stem Cell Research
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles
keywords: Benzimidazole; Chemotherapy; Genome; Germinative cells; Neoblasts; Stem cells; Transcriptome; β-Tubulin