On the importance of targeting parasite stem cells in anti-echinococcosis drug development
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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EDP Sciences
2014-01-01
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| Series: | Parasite |
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| Online Access: | http://dx.doi.org/10.1051/parasite/2014070 |
| _version_ | 1797428478655594496 |
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| author | Brehm Klaus Koziol Uriel |
| author_facet | Brehm Klaus Koziol Uriel |
| author_sort | Brehm Klaus |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T08:59:29Z |
| format | Article |
| id | doaj.art-ad31c8471d834fa38a65cb2ee2230bbe |
| institution | Directory Open Access Journal |
| issn | 1776-1042 |
| language | English |
| last_indexed | 2024-03-09T08:59:29Z |
| publishDate | 2014-01-01 |
| publisher | EDP Sciences |
| record_format | Article |
| series | Parasite |
| spelling | doaj.art-ad31c8471d834fa38a65cb2ee2230bbe2023-12-02T12:14:48ZengEDP SciencesParasite1776-10422014-01-01217210.1051/parasite/2014070parasite140112On the importance of targeting parasite stem cells in anti-echinococcosis drug developmentBrehm KlausKoziol UrielThe 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.http://dx.doi.org/10.1051/parasite/2014070GenomeChemotherapyBeta-tubulinBenzimidazoleStem cellsGerminative cells |
| spellingShingle | Brehm Klaus Koziol Uriel On the importance of targeting parasite stem cells in anti-echinococcosis drug development Parasite Genome Chemotherapy Beta-tubulin Benzimidazole Stem cells Germinative cells |
| title | On the importance of targeting parasite stem cells in anti-echinococcosis drug development |
| title_full | On the importance of targeting parasite stem cells in anti-echinococcosis drug development |
| title_fullStr | On the importance of targeting parasite stem cells in anti-echinococcosis drug development |
| title_full_unstemmed | On the importance of targeting parasite stem cells in anti-echinococcosis drug development |
| title_short | On the importance of targeting parasite stem cells in anti-echinococcosis drug development |
| title_sort | on the importance of targeting parasite stem cells in anti echinococcosis drug development |
| topic | Genome Chemotherapy Beta-tubulin Benzimidazole Stem cells Germinative cells |
| url | http://dx.doi.org/10.1051/parasite/2014070 |
| work_keys_str_mv | AT brehmklaus ontheimportanceoftargetingparasitestemcellsinantiechinococcosisdrugdevelopment AT kozioluriel ontheimportanceoftargetingparasitestemcellsinantiechinococcosisdrugdevelopment |