Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania

Snezhana Akpunarlieva, Stefan Weidt, Dhilia Lamasudin, Christina Naula, David Henderson, Michael Barrett, Karl Burgess, Richard Burchmore

Research output: Contribution to journalArticlepeer-review

Abstract

Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells. Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype.
Original languageEnglish
Pages (from-to)85-98
Number of pages14
JournalJournal of proteomics
Volume155
Early online date29 Dec 2016
DOIs
Publication statusPublished - 23 Feb 2017

Keywords

  • leishmania
  • glucose transporter null mutant
  • metabolic adaptation
  • proteomics
  • metabolomics
  • data integration

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