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On the importance of targeting parasite stem cells in anti-echinococcosis drug development
- Source :
- Parasite, Parasite, Vol 21, p 72 (2014)
- Publication Year :
- 2014
- Publisher :
- EDP Sciences, 2014.
-
Abstract
- 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 chemother- apy, 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 prolif- eration 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.
- Subjects :
- Pluripotent Stem Cells
Germinative cells
Veterinary (miscellaneous)
Cellular differentiation
Drug Evaluation, Preclinical
Innovation for the Management of Echinococcosis. Invited editors: Dominique A. Vuitton, Laurence Millon, Bruno Gottstein and Patrick Giraudoux
Review Article
Stem cells
Echinococcus multilocularis
Benzimidazole
lcsh:Infectious and parasitic diseases
Echinococcosis
Tubulin
parasitic diseases
medicine
Chemotherapy
Animals
Hydroxyurea
lcsh:RC109-216
Molecular Targeted Therapy
Induced pluripotent stem cell
Anthelmintics
Genome
biology
Pteridines
Oncosphere
Genomics
Helminth Proteins
biology.organism_classification
medicine.disease
Virology
Echinococcus
Beta-tubulin
Metacestode
Infectious Diseases
Insect Science
Drug Design
Larva
Immunology
Animal Science and Zoology
Benzimidazoles
Parasitology
Stem cell
Transcriptome
Cell Division
Subjects
Details
- Language :
- English
- ISSN :
- 17761042 and 1252607X
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Parasite
- Accession number :
- edsair.doi.dedup.....5764aac5d3ad75ebf25b46336a057891