title: Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania.
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.
  
  
  
  This paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy.
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: Snezhana
authors.initials: S
authors.lastname: Akpunarlieva
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weidt
authors.affiliation: Department of Cell & Molecular Biology, Faculty of Biotechnology & Biomolecular Sciences, University Putra Malaysia, Malaysia.
authors.forename: Dhilia
authors.initials: D
authors.lastname: Lamasudin
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Naula
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: David
authors.initials: D
authors.lastname: Henderson
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Barrett
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Burgess
authors.affiliation: Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary & Life Sciences, University of Glasgow, UK. Electronic address: richard.burchmore@glasgow.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Burchmore
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D007894:Leishmania mexicana / Q000378:metabolism*; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D020543:Proteome; D015800:Protozoan Proteins
keywords: Data integration; Glucose transporter null mutant; Leishmania; Metabolic adaptation; Metabolomics; Proteomics