A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani

Jessica L. Martin, Phillip Yates, Jan M. Boitz, Dennis Koop, Audrey L. Fulwiler, Maria Belen Cassera, Buddy Ullman, Nicola Carter

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of purine starvation. In order to understand how Leishmania sense and respond to changes in their purine environment, we have exploited several purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring purines, the proliferation of these purine pathway mutants requires specific types or combinations of exogenous purines. By culturing purine pathway mutants in high levels of extracellular purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to purine starvation, we determined that adaptation arises from a surveillance of intracellular purine nucleotide pools rather than from a direct sensing of the extracellular purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a purine-scarce environment.

Original languageEnglish (US)
Pages (from-to)299-313
Number of pages15
JournalMolecular Microbiology
Volume101
Issue number2
DOIs
StatePublished - Jul 1 2016

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Leishmania donovani
Adenine Nucleotides
Starvation
Purines
Leishmania
Nutritional Physiological Phenomena
Purine Nucleotides
purine
Guanine Nucleotides
Growth
Cell Survival
Parasites

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani. / Martin, Jessica L.; Yates, Phillip; Boitz, Jan M.; Koop, Dennis; Fulwiler, Audrey L.; Cassera, Maria Belen; Ullman, Buddy; Carter, Nicola.

In: Molecular Microbiology, Vol. 101, No. 2, 01.07.2016, p. 299-313.

Research output: Contribution to journalArticle

Martin, Jessica L. ; Yates, Phillip ; Boitz, Jan M. ; Koop, Dennis ; Fulwiler, Audrey L. ; Cassera, Maria Belen ; Ullman, Buddy ; Carter, Nicola. / A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani. In: Molecular Microbiology. 2016 ; Vol. 101, No. 2. pp. 299-313.
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