Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-1
pubmed:abstractText
To survive extremely different environments, intracellular parasites require highly adaptable physiological and metabolic systems. Leishmania donovani extracellular promastigotes reside in a glucose-rich, slightly alkaline environment in the sand fly vector alimentary tract. On entry into human macrophage phagolysosomes, promastigotes differentiate into intracellular amastigotes. These cope with an acidic milieu, where glucose is scarce while amino acids are abundant. Here, we use an axenic differentiation model and a novel high-coverage, comparative proteomic methodology to analyze in detail protein expression changes throughout the differentiation process. The analysis identified and quantified 21% of the parasite proteome across 7 time points during differentiation. The data reveal a delayed increase in gluconeogenesis enzymes, coinciding with a decrease in glycolytic capacity. At the same time, beta-oxidation, amino acid catabolism, tricarboxylic acid cycle, mitochondrial respiration chain, and oxidative phosphorylation capacities are all up-regulated. The results indicate that the differentiating parasite shifts from glucose to fatty acids and amino acids as its main energy source. Furthermore, glycerol and amino acids are used as precursors for sugar synthesis, compensating for lack of exogenous sugars. These changes occur while promastigotes undergo morphological transformation. Our findings provide new insight into changes occurring in single-cell organisms during a developmental process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
590-602
pubmed:meshHeading
pubmed-meshheading:17884972-Animals, pubmed-meshheading:17884972-Cell Differentiation, pubmed-meshheading:17884972-Cells, Cultured, pubmed-meshheading:17884972-Citric Acid Cycle, pubmed-meshheading:17884972-Down-Regulation, pubmed-meshheading:17884972-Gastrointestinal Tract, pubmed-meshheading:17884972-Gene Expression Profiling, pubmed-meshheading:17884972-Glycolysis, pubmed-meshheading:17884972-Humans, pubmed-meshheading:17884972-Leishmania, pubmed-meshheading:17884972-Macrophages, pubmed-meshheading:17884972-Mitochondria, pubmed-meshheading:17884972-Oxidation-Reduction, pubmed-meshheading:17884972-Pentose Phosphate Pathway, pubmed-meshheading:17884972-Phosphorylation, pubmed-meshheading:17884972-Protein Biosynthesis, pubmed-meshheading:17884972-Psychodidae, pubmed-meshheading:17884972-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Retooling Leishmania metabolism: from sand fly gut to human macrophage.
pubmed:affiliation
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't