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

Tamara Olenyik, Caslin Gilroy, Buddy Ullman

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 2011

Fingerprint

Leishmania donovani
Ornithine Decarboxylase
Putrescine
Virulence
Polyamines
Drinking Water
Parasites
Eflornithine
Phagosomes
Visceral Leishmaniasis
Oral Administration
Macrophages
Growth
Infection
Pharmaceutical Preparations
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

Oral putrescine restores virulence of ornithine decarboxylase-deficient Leishmania donovani in mice. / Olenyik, Tamara; Gilroy, Caslin; Ullman, Buddy.

In: Molecular and Biochemical Parasitology, Vol. 176, No. 2, 04.2011, p. 109-111.

Research output: Contribution to journalArticle

Olenyik, Tamara ; Gilroy, Caslin ; Ullman, Buddy. / Oral putrescine restores virulence of ornithine decarboxylase-deficient Leishmania donovani in mice. In: Molecular and Biochemical Parasitology. 2011 ; Vol. 176, No. 2. pp. 109-111.
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