Induction of a Stringent Metabolic Response in Intracellular Stages of Leishmania mexicana Leads to Increased Dependence on Mitochondrial Metabolism
Eleanor C Saunders, William W Ng, Joachim Kloehn, Jennifer M Chambers, Milica Ng, Malcolm J McConville
PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2014
Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13)C-stable isotope resolved metabolomics and (2)H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and..View full abstract
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Awarded by Australian National Health and Medical Research Council (NHMRC)
This work was supported by a Australian National Health and Medical Research Council (NHMRC) grant (APP1006023). WN was supported by an Australian Postgraduate Award. MJM is a NHMRC Principal Research Fellow (APP566643). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.