Academic Journal
Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels
| العنوان: | Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels |
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| المؤلفون: | Becker, John V.W., Mtwisha, Linda, Crampton, Bridget Genevieve, Stoychev, Stoyan H., Van Brummelen, Anna Catharina, Reeksting, Shaun Bernard, Louw, Abraham Izak, Birkholtz, Lyn-Marie, Mancama, Dalu |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2010 |
| المجموعة: | University of Pretoria: UPSpace |
| مصطلحات موضوعية: | Plasmodium falciparum, Spermidine, Polyamines, Malaria -- Chemotherapy, Antimalarials -- Research, Drug resistance |
| الوصف: | BACKGROUND: Plasmodium falciparum, the causative agent of severe human malaria, has evolved to become resistant to previously successful antimalarial chemotherapies, most notably chloroquine and the antifolates. The prevalence of resistant strains has necessitated the discovery and development of new chemical entities with novel modes-of-action. Although much effort has been invested in the creation of analogues based on existing drugs and the screening of chemical and natural compound libraries, a crucial shortcoming in current Plasmodial drug discovery efforts remains the lack of an extensive set of novel, validated drug targets. A requirement of these targets (or the pathways in which they function) is that they prove essential for parasite survival. The polyamine biosynthetic pathway, responsible for the metabolism of highly abundant amines crucial for parasite growth, proliferation and differentiation, is currently under investigation as an antimalarial target. Chemotherapeutic strategies targeting this pathway have been successfully utilized for the treatment of Trypanosomes causing West African sleeping sickness. In order to further evaluate polyamine depletion as possible antimalarial intervention, the consequences of inhibiting P. falciparum spermidine synthase (PfSpdSyn) were examined on a morphological, transcriptomic, proteomic and metabolic level. RESULTS: Morphological analysis of P. falciparum 3D7 following application of the PfSpdSyn inhibitor cyclohexylamine confirmed that parasite development was completely arrested at the early trophozoite stage. This is in contrast to untreated parasites which progressed to late trophozoites at comparable time points. Global gene expression analyses confirmed a transcriptional arrest in the parasite. Several of the differentially expressed genes mapped to the polyamine biosynthetic and associated metabolic pathways. Differential expression of corresponding parasite proteins involved in polyamine biosynthesis was also observed. Most notably, uridine ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1471-2164 |
| Relation: | http://hdl.handle.net/2263/14743; Becker et al., Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels BMC Genomics 2010, 11:235. [http://www.biomedcentral.com/bmcgenomics/] |
| DOI: | 10.1186/1471-2164-11-235 |
| الاتاحة: | http://hdl.handle.net/2263/14743 https://doi.org/10.1186/1471-2164-11-235 |
| Rights: | © 2010 Becker et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| رقم الانضمام: | edsbas.B5BA7F9A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712164 |
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| DOI: | 10.1186/1471-2164-11-235 |