Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania

Akpunarlieva, S., Weidt, S., Lamasudin, D., Naula, C., Henderson, D., Barrett, M. , Burgess, K. and Burchmore, R. (2017) Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania. Journal of Proteomics, 155, pp. 85-98. (doi:10.1016/j.jprot.2016.12.009) (PMID:28040509)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Weidt, Dr Stefan and Naula, Dr Christina and Burchmore, Dr Richard and Burgess, Dr Karl and Barrett, Professor Michael
Authors: Akpunarlieva, S., Weidt, S., Lamasudin, D., Naula, C., Henderson, D., Barrett, M., Burgess, K., and Burchmore, R.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Proteomics
Publisher:Elsevier
ISSN:1874-3919
ISSN (Online):1874-3919
Published Online:29 December 2016

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
470561DTC in cell and proteomic technologies (continuation)Jonathan CooperEngineering & Physical Sciences Research Council (EPSRC)EP/F500424/1ENG - BIOMEDICAL ENGINEERING