Leishmania mexicana can utilize amino acids as major carbon sources in macrophages but not in animal models

Eleanor C. Saunders, Thomas Naderer, Jenny Chambers, Scott Landfear, Malcolm J. Mcconville

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Leishmania parasites target macrophages in their mammalian hosts and proliferate within the mature phagolysosome compartment of these cells. Intracellular amastigote stages are dependent on sugars as a major carbon source in vivo, but retain the capacity to utilize other carbon sources. To investigate whether amastigotes can switch to using other carbon sources, we have screened for suppressor strains of the L. mexicana Δlmxgt1-3 mutant which lacks the major glucose transporters LmxGT1-3. We identified a novel suppressor line (Δlmxgt1-3s2) that has restored growth in rich culture medium and virulence in ex vivo infected macrophages, but failed to induce lesions in mice. Δlmxgt1-3s2 amastigotes had lower rates of glucose utilization than the parental line and primarily catabolized non-essential amino acids. The increased mitochondrial metabolism of this line was associated with elevated levels of intracellular reactive oxygen species, as well as increased sensitivity to inhibitors of the tricarboxylic acid (TCA) cycle, including nitric oxide. These results suggest that hardwired sugar addiction of Leishmania amastigotes contributes to the intrinsic resistance of this stage to macrophage microbicidal processes in vivo, and that these stages have limited capacity to switch to using other carbon sources.

Original languageEnglish (US)
JournalMolecular Microbiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Leishmania mexicana
Carbon
Animal Models
Macrophages
Amino Acids
Leishmania
Phagosomes
Citric Acid Cycle
Facilitative Glucose Transport Proteins
Virulence
Culture Media
Reactive Oxygen Species
Nitric Oxide
Parasites
Glucose
Growth

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Leishmania mexicana can utilize amino acids as major carbon sources in macrophages but not in animal models. / Saunders, Eleanor C.; Naderer, Thomas; Chambers, Jenny; Landfear, Scott; Mcconville, Malcolm J.

In: Molecular Microbiology, 01.01.2018.

Research output: Contribution to journalArticle

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