Oral putrescine restores virulence of ornithine decarboxylase-deficient Leishmania donovani in mice

Tamara Olenyik, Caslin Gilroy, Buddy Ullman

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)109-111
Number of pages3
JournalMolecular and Biochemical Parasitology
Volume176
Issue number2
DOIs
StatePublished - Apr 1 2011

Keywords

  • Leishmania donovani
  • Ornithine decarboxylase
  • Polyamines
  • Putrescine
  • α-Difluoromethylornithine

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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