Abstract |
Administration of putrescine as a 1% solution in the drinking water ameliorated the profound loss of virulence exhibited by ornithine decarboxylase (ODC) deficient Leishmania donovani in mice. Furthermore, supplying α- difluoromethylornithine, an ODC inhibitor, at 2% in the drinking water reduced but did not eliminate infection with wild type L. donovani in the mouse model. Taken collectively, these findings: (1) demonstrate that oral putrescine can access the phagolysosome of macrophages in which the parasite resides in mice; (2) establish that the loss of virulence due to the Δodc lesion is a consequence of the inability of the mutant parasite to synthesize sufficient polyamines de novo; (3) imply that the L. donovani amastigote cannot access host polyamines in sufficient amounts for survival and growth; (4) and validate ODC as a drug target, although oral administration of DFMO is an unlikely therapeutic paradigm for visceral leishmaniasis.
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Authors | Tamara Olenyik, Caslin Gilroy, Buddy Ullman |
Journal | Molecular and biochemical parasitology
(Mol Biochem Parasitol)
Vol. 176
Issue 2
Pg. 109-11
(Apr 2011)
ISSN: 1872-9428 [Electronic] Netherlands |
PMID | 21182873
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2011 Elsevier B.V. All rights reserved. |
Chemical References |
- Enzyme Inhibitors
- Ornithine Decarboxylase Inhibitors
- Water
- Ornithine Decarboxylase
- Putrescine
- Eflornithine
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Topics |
- Administration, Oral
- Animals
- Disease Models, Animal
- Eflornithine
(pharmacology, therapeutic use)
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Female
- Leishmania donovani
(drug effects, genetics, metabolism)
- Leishmaniasis, Visceral
(drug therapy, parasitology)
- Macrophages
(drug effects, metabolism)
- Mice
- Mice, Inbred BALB C
- Molecular Targeted Therapy
- Organisms, Genetically Modified
(genetics, metabolism)
- Ornithine Decarboxylase
(genetics, metabolism)
- Ornithine Decarboxylase Inhibitors
- Phagosomes
(drug effects, metabolism)
- Putrescine
(metabolism, pharmacology)
- Virulence
(drug effects, genetics)
- Water
(chemistry)
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