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African Sleeping Sickness (african + sleeping_sickness)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Dichlorodiphenyltrichloroethane in the aquatic ecosystem of the Okavango Delta, Botswana, South Africa

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2003
Bontle Mbongwe
Abstract Concentrations of DDT and its metabolites were measured in water, plants, invertebrates, and fish from lagoons in the Okavango Delta, Botswana (Africa), where DDT has been used for approximately 50 years. The sampling area was sectioned to distinguish spraying for malaria and for African sleeping sickness. Average concentrations of total DDT (sum of DDT and its metabolites) in the Okavango ranged from 0.009 ng/L in water to 18.76 ng/g wet weight in fish. These levels are approximately 1% of those found in piscivorous fish from temperate North America. The dichlorodiphenyl ethylene (DDE) metabolite was the most abundant fraction of total DDT. Although total DDT concentrations were higher in areas treated for malaria than areas treated for sleeping sickness, these concentrations were likely driven by factors other than the historic application of the pesticide. Equilibration with air concentrations is the most likely explanation for these levels. Since the mean annual temperature exceeds the temperature of vaporization of DDT, this research points to the need for reliable transport models. Our results showed that total DDT concentration in fish was best explained by lipid content of the fish and trophic position inferred by ,15N, regardless of DDT application history in those areas. The reservoir above Gaborone Dam, an area downstream of the Okavango but where DDT had not been used, was sampled to compare total DDT levels to the treated areas. The two species (a herbivorous threespot talapia and the omnivorous sharptooth catfish) from Gaborone had levels higher than those found in the Okavango Delta, but these differences can again be explained using trophic position inferred by ,15N rather than by fish size or location. [source]

The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei

MOLECULAR MICROBIOLOGY, Issue 6 2010
Simon A. Young
Summary Sphingomyelin is the main sphingolipid in Trypanosoma brucei, the causative agent of African sleeping sickness. In vitro and in vivo characterization of the T. brucei neutral sphingomyelinase demonstrates that it is directly involved in sphingomyelin catabolism. Gene knockout studies in the bloodstream form of the parasite indicate that the neutral sphingomyelinase is essential for growth and survival, thus highlighting that the de novo biosynthesis of ceramide is unable to compensate for the loss of sphingomyelin catabolism. The phenotype of the conditional knockout has given new insights into the highly active endocytic and exocytic pathways in the bloodstream form of T. brucei. Hence, the formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface. This directly influences the corresponding rate of endocytosis, via the recycling endosomes, of pre-existing cell surface variant surface glycoprotein. The trypanosomes use this coupled endocytic and exocytic mechanism to maintain the cell density of its crucial variant surface glycoprotein protective coat. TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis. [source]

The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositol

MOLECULAR MICROBIOLOGY, Issue 1 2006
Kirstee L. Martin
Summary In bloodstream-form Trypanosoma brucei (the causative agent of African sleeping sickness) the glycosylphosphatidylinositol (GPI) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. The conundrum that GPI anchors could not be in vivo labelled with [3H]-inositol led us to hypothesize that de novo synthesis was responsible for supplying myo -inositol for phosphatidylinositol (PI) destined for GPI synthesis. The rate-limiting step of the de novo synthesis is the isomerization of glucose 6-phosphate to 1- d -myo -inositol-3-phosphate, catalysed by a 1- d -myo -inositol-3-phosphate synthase (INO1). When grown under non-permissive conditions, a conditional double knockout demonstrated that INO1 is an essential gene in bloodstream-form T. brucei. It also showed that the de novo synthesized myo -inositol is utilized to form PI, which is preferentially used in GPI biosynthesis. We also show for the first time that extracellular myo- inositol can in fact be used in GPI formation although to a limited extent. Despite this, extracellular inositol cannot compensate for the deletion of INO1. Supporting these results, there was no change in PI levels in the conditional double knockout cells grown under non-permissive conditions, showing that perturbation of growth is due to a specific lack of de novo synthesized myo -inositol and not a general inositol-less death. These results suggest that there is a distinction between de novo synthesized myo -inositol and that from the extracellular environment. [source]

Geobacillus stearothermophilus 6-phosphogluconate dehydrogenase complexed with 6-phosphogluconate

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2009
Scott Cameron
Two crystal structures of recombinant Geobacillus stearothermophilus 6-phosphogluconate dehydrogenase (Gs6PDH) in complex with the substrate 6-phosphogluconate have been determined at medium resolution. Gs6PDH shares significant sequence identity and structural similarity with the enzymes from Lactococcus lactis, sheep liver and the protozoan parasite Trypanosoma brucei, for which a range of structures have previously been reported. Comparisons indicate that amino-acid sequence conservation is more pronounced in the two domains that contribute to the architecture of the active site, namely the N-terminal and C-terminal domains, compared with the central domain, which is primarily involved in the subunit,subunit associations required to form a stable dimer. The active-site residues are highly conserved, as are the interactions with the 6-phosphogluconate. There is interest in 6PDH as a potential drug target for the protozoan parasite T. brucei, the pathogen responsible for African sleeping sickness. The recombinant T. brucei enzyme has proven to be recalcitrant to enzyme,ligand studies and a surrogate protein might offer new opportunities to investigate and characterize 6PDH inhibitors. The high degree of structural similarity, efficient level of expression and straightforward crystallization conditions mean that Gs6PDH may prove to be an appropriate model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species. [source]