| tsetse ep protein protects the fly midgut from trypanosome establishment. | african trypanosomes undergo a complex developmental process in their tsetse fly vector before transmission back to a vertebrate host. typically, 90% of fly infections fail, most during initial establishment of the parasite in the fly midgut. the specific mechanism(s) underpinning this failure are unknown. we have previously shown that a glossina-specific, immunoresponsive molecule, tsetse ep protein, is up regulated by the fly in response to gram-negative microbial challenge. here we show by kn ... | 2010 | 20221444 |
| a search for trypanosoma brucei rhodesiense diagnostic antigens by proteomic screening and targeted cloning. | the only available diagnostic method for east african trypanosomiasis is light microscopy of blood samples. a simple immunodiagnostic would greatly aid trypanosomiasis control. | 2010 | 20224787 |
| chemical composition of the essential oils of two citrus species and their biological activities. | essential oils obtained by hydrodistillation of the fruit rinds of citrus jambhiri lush. (rough lemon) and c. pyriformis hassk (ponderosa lemon) were analyzed by capillary gas chromatography (glc/fid) and gas chromatography-mass spectrometry (glc/ms). a total of 94 compounds were unambiguously identified from the oils and the (hexane/ether) extracts of the rind and juices representing 98.55% and 97.98% of the total oil composition. the main component of both oils was d-limonene (92.48% and 75.56 ... | 2010 | 20225661 |
| polo-like kinase guides cytokinesis in trypanosoma brucei through an indirect means. | polo-like kinase in trypanosoma brucei (tbplk) is confined to the flagellum attachment zone (faz) and regulates only cytokinetic initiation. however, it apparently diffuses into the cytoplasm before the trans-localization of chromosomal passenger complex (cpc) from the midzone of central spindle to faz, which is known to be required for initiating cytokinesis. synchronized t. brucei procyclic cells treated with a tbplk inhibitor, gw843682x (gw), in late s phase were found to go through a full ce ... | 2010 | 20228202 |
| nuclear dbf-2-related kinases are essential regulators of cytokinesis in bloodstream stage trypanosoma brucei. | nuclear dbf-2-related (ndr) kinases are essential regulators of cell cycle progression, growth, and development in many organisms and are activated by the binding of an mps one binder (mob) protein partner, autophosphorylation, and phosphorylation by an upstream ste20 family kinase. in the protozoan parasite, trypanosoma brucei, the causative agent of human african trypanosomiasis, the ndr kinase, pk50, is expressed in proliferative life cycle stages and was shown to complement a yeast ndr kinas ... | 2010 | 20231285 |
| antitrypanosomal cyclic polyketide peroxides from the australian marine sponge plakortis sp. | bioassay-guided fractionation of the crude extract from the australian marine sponge plakortis sp. led to the isolation of two new cyclic polyketide peroxides, 11,12-didehydro-13-oxo-plakortide q (1) and 10-carboxy-11,12,13,14-tetranor-plakortide q (2). antitrypanosomal studies showed that compound 1 had an ic(50) value of 49 nm against trypanosoma brucei brucei, and compound 2, where a carboxylic acid is present in the side chain, had a 20-fold reduction of activity. 11,12-didehydro-13-oxo-plak ... | 2010 | 20235550 |
| developmental forms of trypanosoma brucei in the saliva of glossina pallidipes and glossina austeni. | | 1947 | 20249284 |
| a comparative proteomic analysis reveals a new bi-lobe protein required for bi-lobe duplication and cell division in trypanosoma brucei. | a golgi-associated bi-lobed structure was previously found to be important for golgi duplication and cell division in trypanosoma brucei. to further understand its functions, comparative proteomics was performed on extracted flagellar complexes (including the flagellum and flagellum-associated structures such as the basal bodies and the bi-lobe) and purified flagella to identify new bi-lobe proteins. a leucine-rich repeats containing protein, tblrrp1, was characterized as a new bi-lobe component ... | 2010 | 20300570 |
| selection of reference genes for mrna quantification in trypanosoma brucei. | internal normalization is an established procedure that is necessary for accurate and reliable quantification of differentially regulated mrnas. the profound changes of gene expression in parasitic life cycles pose a particular challenge on selection of appropriate reference genes for normalization, most importantly when using quantitative real time pcr (qpcr). here we use the ranking algorithm implemented in the genorm application to identify suitable trypanosoma brucei reference genes for comp ... | 2010 | 20302889 |
| assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi. | human african trypanosomiasis (hat, commonly known as african sleeping sickness) is categorized as a neglected disease, as it afflicts >50,000 people annually in sub-saharan africa, and there are few formal programs in the world focused on drug discovery approaches for this disease. in this study, we examined the crude extracts of two fungal strains (aspergillus fumigatus and nectria inventa) isolated from deep water sediment which provided >99% growth inhibition at 1microg/ml of trypanosoma bru ... | 2010 | 20303767 |
| total synthesis, antiprotozoal and cytotoxicity activities of rhuschalcone vi and analogs. | the total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone vi, is described starting from simple and available resorcinol and 4-hydroxybenzaldehyde. key steps include the solvent-free aldol syntheses of chalcones, and the successful application of the suzuki-miyaura coupling reaction in the synthesis of bichalcones. the present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone vi. some of the bichalcones showed moder ... | 2010 | 20304658 |
| antitrypanosomal effects of petroleum ether, chloroform and methanol extracts of artemisia maciverae linn. | petroleum ether, chloroform and methanol extracts of a. maciverae were studied in vitro and in vivo for activity against trypanosoma brucei brucei in swiss albino mice. thereafter, the chloroform extract which showed the highest activity in both in vitro and in vivo assessments was subjected to bioassay-guided fractionation. the crude extracts and the fractions of the chloroform extract of a. maciverae were screened for phytochemicals and secondary metabolites. combined fractions 54-57 of this e ... | 2009 | 20329702 |
| trypanosoma brucei infection in asymptomatic greater kudus (tragelaphus strepsiceros) on a game ranch in zambia. | trypomastogotes of trypanosoma brucei were detected from 4 asymptomatic kudus (tragelaphus strepsiceros) on a game ranch located approximately 45 km north east of lusaka, zambia. blood smears examined from 14 wildlife species comprising of the impala (aepyceros melampus), kafue lechwe (kobus leche kafuensis), sable antelope (hippotragus niger), tsessebe (damaliscus lunatus), warthog (phacochoerus aethiopicus), puku (kobus vardoni), zebra (equus burchelli), waterbuck (kobus ellipsiprymnus), bushb ... | 2010 | 20333288 |
| lipid remodelling of glycosylphosphatidylinositol (gpi) glycoconjugates in procyclic-form trypanosomes: biosynthesis and processing of gpis revisited. | the african trypanosome, trypanosoma brucei, has been used as a model to study the biosynthesis of gpi (glycosylphosphatidylinositol) anchors. in mammalian (bloodstream)-form parasites, diacyl-type gpi precursors are remodelled in their lipid moieties before attachment to variant surface glycoproteins. in contrast, the gpi precursors of insect (procyclic)-form parasites, consisting of lyso-(acyl)pi (inositol-acylated acyl-lyso-phosphatidylinositol) species, remain unaltered before protein attach ... | 2010 | 20345369 |
| histone h3 trimethylated at lysine 4 is enriched at probable transcription start sites in trypanosoma brucei. | recent studies have identified histone modifications and suggested a role for epigenetic gene regulation in trypanosoma brucei. the histone modification h4k10ac and histone variants h2az and h2bv localize to probable sites of transcription initiation. although all t. brucei histones have very evolutionarily divergent n-terminal tails, histone h3 shows conservation with other eukaryotic organisms in 6 of 8 amino acids encompassing lysine 4. tri-methylation of h3k4 is generally associated with tra ... | 2010 | 20347883 |
| clock gene expression during chronic inflammation induced by infection with trypanosoma brucei brucei in rats. | african sleeping sickness is characterized by alterations in rhythmic functions. it is not known if the disease affects the expression of clock genes, which are the molecular basis for rhythm generation. we used a chronic rat model of experimental sleeping sickness, caused by the extracellular parasite trypanosoma brucei brucei (tb brucei), to study the effects on clock gene expression. in tissue explants of pituitary glands from period1-luciferase (per1-luc) transgenic rats infected with tb bru ... | 2010 | 20348460 |
| [cloning, expression, purification and activity assay of trypanosoma brucei phenylalanyl-trna synthetase in escherichia coli]. | phenylalany--trna synthetase is a key enzyme for protein synthesis in trypanosoma. its validation as an inhibition. target will enable the development of a new generation of anti-trypanosoma drugs. however, little is known about the isolation of the trypanosoma phenylalanyl-trna synthetase. here we report the cloning, expression, purification, and activity assay of phenylalanyl-trna synthetase from trypanosoma brucei in escherichia coli host. we co-cloned the alpha-subunit and beta-subunit of ph ... | 2010 | 20353103 |
| drug discovery: fat-free proteins kill parasites. | | 2010 | 20360728 |
| n-myristoyltransferase inhibitors as new leads to treat sleeping sickness. | african sleeping sickness or human african trypanosomiasis, caused by trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suit ... | 2010 | 20360736 |
| mechanism of u insertion rna editing in trypanosome mitochondria: the bimodal tutase activity of the core complex. | expression of the trypanosomal mitochondrial genome requires the insertion and deletion of uridylyl residues at specific sites in pre-mrnas. ret2 terminal uridylyl transferase is an integral component of the rna editing core complex (recc) and is responsible for the guide-rna-dependent u insertion reaction. by analyzing rna-interference-based knock-in trypanosoma brucei cell lines, purified editing complex, and individual protein, we have investigated ret2's association with the recc. in additio ... | 2010 | 20362585 |
| processing of a phosphoglycerate kinase reporter mrna in trypanosoma brucei is not coupled to transcription by rna polymerase ii. | capping of mrnas is strictly coupled to rna polymerase ii transcription and there is evidence, mainly from metazoans, that other steps in pre-mrna processing show a similar linkage. in trypanosomes, however, the mrna cap is supplied by a trans spliced leader sequence. thus pre-mrnas transcribed by rna polymerase i are capped by trans splicing, and translation-competent transgenic mrnas can be produced by rna polymerase i and t7 rna polymerase so long as the primary transcript has a splice accept ... | 2010 | 20363263 |
| progressive meningoencephalitis in a sudanese immigrant. | | 2010 | 20367592 |
| late-stage human african trypanosomiasis in a sudanese refugee. | a 19-year-old sudanese woman, who had lived for about a decade in ugandan refugee camps, was referred for investigation of a 12-month history of a generalised rash. two months later, her condition had deteriorated to include cachexia and drowsiness. despite initial negative findings on investigation, human african trypanosomiasis (hat) was suspected, and parasites were found in a double-centrifuged sample of cerebrospinal fluid. eflornithine, the appropriate drug for treatment of late-stage dise ... | 2010 | 20367593 |
| expression of the inhibitory cd200 receptor is associated with alternative macrophage activation. | classical macrophage activation is inhibited by the cd200 receptor (cd200r). here, we show that cd200r expression was specifically induced on human in vitro polarized macrophages of the alternatively activated m2a subtype, generated by incubation with il-4 or il-13. in mice, peritoneal m2 macrophages, elicited during infection with the parasites taenia crassiceps or trypanosoma brucei brucei, expressed increased cd200r levels compared to those derived from uninfected mice. however, in vitrostimu ... | 2010 | 20375636 |
| in vitro and in vivo antiprotozoal activities of bispolides and their derivatives. | | 2010 | 20379214 |
| antiplasmodial, antitrypanosomal, and cytotoxic activities of prenylated flavonoids isolated from the stem bark of artocarpus styracifolius. | in continuation of our efforts to find new antimalarial drugs, a systematic in vitro evaluation using a chloroquine resistant strain of plasmodium falciparum (fcb1) was undertaken on extracts prepared from various parts of vietnamese plants. the ethyl acetate extract obtained from the stem bark of artocarpus styracifolius (moraceae) exhibited strong antiplasmodial activity (87 % at 10 µg/ml) whereas weak cytotoxicity was observed in a human fibroblast cell line (mrc-5). phytochemical investigati ... | 2010 | 20379954 |
| lipid metabolism in trypanosoma brucei. | trypanosoma brucei membranes consist of all major eukaryotic glycerophospholipid and sphingolipid classes. these are de novo synthesized from precursors obtained either from the host or from catabolised endocytosed lipids. in recent years, substantial progress has been made in the molecular and biochemical characterisation of several of these lipid biosynthetic pathways, using gene knockout or rna interference strategies or by enzymatic characterization of individual reactions. together with the ... | 2010 | 20382188 |
| genome-wide analysis of mrna abundance in two life-cycle stages of trypanosoma brucei and identification of splicing and polyadenylation sites. | transcription of protein-coding genes in trypanosomes is polycistronic and gene expression is primarily regulated by post-transcriptional mechanisms. sequence motifs in the untranslated regions regulate mrna trans-splicing and rna stability, yet where utrs begin and end is known for very few genes. we used high-throughput rna-sequencing to determine the genome-wide steady-state mrna levels ('transcriptomes') for approximately 90% of the genome in two stages of the trypanosoma brucei life cycle c ... | 2010 | 20385579 |
| structural characterization of cyp51 from trypanosoma cruzi and trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. | chagas disease is the leading cause of heart failure in latin america. current drug therapy is limited by issues of both efficacy and severe side effects. trypansoma cruzi, the protozoan agent of chagas disease, is closely related to two other major global pathogens, leishmania spp., responsible for leishmaniasis, and trypansoma brucei, the causative agent of african sleeping sickness. both t. cruzi and leishmania parasites have an essential requirement for ergosterol, and are thus vulnerable to ... | 2010 | 20386598 |
| domestic animals as potential reservoir hosts of trypanosoma brucei gambiense in sleeping sickness foci in cameroon. | an explanation of the endemic nature and/or the resurgence of human african trypanosomiasis (hat) in the historic foci in west and central africa may be the existence of an animal reservoir. in some hat foci, pigs were found infected by trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. this study aims to determine the prevalence of t. b. gambiense in domestic animal species (goat, sheep, pig and dog) commonly found in the four active hat foci ... | 2010 | 20387740 |
| anti-parasitic compounds from streptomyces sp. strains isolated from mediterranean sponges. | actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. in this study, we report on the isolation of streptomyces sp. strains from mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolo ... | 2010 | 20390111 |
| structure of the trypanosoma brucei p22 protein, a cytochrome oxidase subunit ii-specific rna-editing accessory factor. | kinetoplastid rna (k-rna) editing is a complex process in the mitochondria of kinetoplastid protozoa, including trypanosoma brucei, that involves the guide rna-directed insertion and deletion of uridines from precursor-mrnas to produce mature, translatable mrnas. k-rna editing is performed by multiprotein complexes called editosomes. additional non-editosome components termed k-rna-editing accessory factors affect the extent of editing of specific rnas or classes of rnas. the t. brucei p22 prote ... | 2010 | 20392699 |
| the trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill. | humans have developed a particular innate immunity system against african trypanosomes, and only two trypanosoma brucei clones (t. b. gambiense, t. b. rhodesiense) can resist this defence and cause sleeping sickness. the main players of this immunity are the primate-specific apolipoprotein l-i (apol1) and haptoglobin-related protein (hpr). these proteins are both associated with two serum complexes, a minor subfraction of hdls and an igm/apolipoprotein a-i (apoa1) complex, respectively, termed t ... | 2010 | 20398209 |
| the essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of trypanosoma brucei. | 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 lo ... | 2010 | 20398210 |
| structure of the mitochondrial editosome-like complex associated tutase 1 reveals divergent mechanisms of utp selection and domain organization. | rna uridylylation reactions catalyzed by terminal uridylyl transferases (tutases) play critical roles in the formation of the mitochondrial transcriptome in trypanosomes. two mitochondrial rna editing tutases have been described: rna editing tutase 1 catalyzes guide rna, ribosomal rna, and mrna 3'-uridylylation, and rna editing tutase 2 acts as a subunit of the rna editing core complex (also referred to as the 20s editosome) to perform guided u-insertion mrna editing. although rna editing tutase ... | 2010 | 20403364 |
| synthesis and antiprotozoal activity of 2,5-bis[amidinoaryl]thiazoles. | seven novel diamidino 2,5-bis(aryl)thiazoles (5a-g) were synthesized and evaluated against trypanosoma brucei rhodensiense (t. b. r.) and plasmodium falciparum (p. f.). the diamidines were obtained directly from the corresponding bis-nitriles (4a-g) by the action of lithium bis(trimethylsilyl)amide. the bis-nitriles 4a-f were synthesized in four steps starting with the stille coupling of 2-tributyltinthiazole with the appropriate cyanoaryl halide. the bis-nitrile 5g was obtained by the palladium ... | 2010 | 20403703 |
| a target-based high throughput screen yields trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. | the parasitic protozoan trypanosoma brucei utilizes glycolysis exclusively for atp production during infection of the mammalian host. the first step in this metabolic pathway is mediated by hexokinase (tbhk), an enzyme essential to the parasite that transfers the gamma-phospho of atp to a hexose. here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed tbhk1, one of two tbhks expressed by t. brucei, using a high throughput screening assay. | 2010 | 20405000 |
| approaches for functional analysis of flagellar proteins in african trypanosomes. | the eukaryotic flagellum is a highly conserved organelle serving motility, sensory, and transport functions. although genetic, genomic, and proteomic studies have led to the identification of hundreds of flagellar and putative flagellar proteins, precisely how these proteins function individually and collectively to drive flagellum motility and other functions remains to be determined. in this chapter we provide an overview of tools and approaches available for studying flagellum protein functio ... | 2009 | 20409810 |
| tools for analyzing intraflagellar transport in trypanosomes. | african trypanosomes are evolutionary-divergent eukaryotes responsible for sleeping sickness. they duplicate their single flagellum while maintaining the old one, providing a unique model to examine mature and elongating flagella in the same cell. like in most eukaryotes, the trypanosome flagellum is constructed by addition of novel subunits at its distal end via the action of intraflagellar transport (ift). almost all genes encoding ift proteins and motors are conserved in trypanosomes and rela ... | 2009 | 20409811 |
| isolation, phylogenetic analysis and anti-infective activity screening of marine sponge-associated actinomycetes. | terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. in this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore ras mohamed (egypt) and from rovinj (croatia). phylogenetic characterization of the isolates based on 16s rrna gene sequencing supported their assignment to 18 different actinomycete genera representing seven differen ... | 2010 | 20411105 |
| calflagin inhibition prolongs host survival and suppresses parasitemia in trypanosoma brucei infection. | african trypanosomes express a family of dually acylated, ef-hand calcium-binding proteins called the calflagins. these proteins associate with lipid raft microdomains in the flagellar membrane, where they putatively function as calcium signaling proteins. here we show that these proteins bind calcium with high affinity and that their expression is regulated during the life cycle stage of the parasite, with protein levels approximately 10-fold higher in the mammalian bloodstream form than in the ... | 2010 | 20418379 |
| tbprmt6 is a type i protein arginine methyltransferase that contributes to cytokinesis in trypanosoma brucei. | arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (prmts). in saccharomyces cerevisiae and mammals, this modification affects multiple cellular processes, such as chromatin remodeling leading to transcriptional regulation, rna processing, dna repair, and cell signaling. the protozoan parasite trypanosoma brucei possesses five putative prmts in its genome. this is a large number of prmts relative to other u ... | 2010 | 20418380 |
| antitrypanosomal peptaibiotics, trichosporins b-viia and b-viib, produced by trichoderma polysporum fki-4452. | | 2010 | 20431618 |
| cross-resistance to nitro drugs and implications for treatment of human african trypanosomiasis. | the success of nifurtimox-eflornithine combination therapy (nect) for the treatment of human african trypanosomiasis (hat) has renewed interest in the potential of nitro drugs as chemotherapeutics. in order to study the implications of the more widespread use of nitro drugs against these parasites, we examined the in vivo and in vitro resistance potentials of nifurtimox and fexinidazole and its metabolites. following selection in vitro by exposure to increasing concentrations of nifurtimox, tryp ... | 2010 | 20439607 |
| the fe/s cluster assembly protein isd11 is essential for trna thiolation in trypanosoma brucei. | fe/s clusters are part of the active site of many enzymes and are essential for cell viability. in eukaryotes the cysteine desulfurase nfs (iscs) donates the sulfur during fe/s cluster assembly and was thought sufficient for this reaction. moreover, nfs is indispensable for trna thiolation, a modification generally required for trna function and protein synthesis. recently, isd11 was discovered as an integral part of the nfs activity at an early step of fe/s cluster assembly. here we show, using ... | 2010 | 20442400 |
| genome-wide in silico screen for ccch-type zinc finger proteins of trypanosoma brucei, trypanosoma cruzi and leishmania major. | ccch type zinc finger proteins are rna binding proteins with regulatory functions at all stages of mrna metabolism. the best-characterized member, tritetraproline (ttp), binds to au rich elements in 3' utrs of unstable mrnas, mediating their degradation. in kinetoplastids, ccch type zinc finger proteins have been identified as being involved in the regulation of the life cycle and possibly the cell cycle. to date, no systematic listing of ccch proteins in kinetoplastids is available. | 2010 | 20444260 |
| the trypanosoma brucei life cycle switch tbptp1 is structurally conserved and dephosphorylates the nucleolar protein nopp44/46. | trypanosoma brucei adapts to changing environments as it cycles through arrested and proliferating stages in the human and tsetse fly hosts. changes in protein tyrosine phosphorylation of several proteins, including nopp44/46, accompany t. brucei development. moreover, inactivation of t. brucei protein-tyrosine phosphatase 1 (tbptp1) triggers differentiation of bloodstream stumpy forms into tsetse procyclic forms through unknown downstream effects. here, we link these events by showing that nopp ... | 2010 | 20444707 |
| a fluorescence-based reporter substrate for monitoring rna editing in trypanosomatid pathogens. | rna editing regulates mitochondrial gene expression in trypanosomatid pathogens by creating functional mrnas. it is catalyzed by a multi-protein complex (the editosome), and is found to be essential in both insect stage and mammalian blood stream form of trypanosoma brucei. this particular form of rna editing is unique to trypanosomatids, and thus provides a suitable drug target in trypanosomatid pathogens. here, we demonstrate the feasibility of a rapid and sensitive fluorescence-based reporter ... | 2010 | 20444864 |
| trnasec is transcribed by rna polymerase ii in trypanosoma brucei but not in humans. | nuclear-encoded trnas are universally transcribed by rna polymerase iii (pol-iii) and contain intragenic promoters. transcription of vertebrate trna(sec) however requires extragenic promoters similar to pol-iii transcribed u6 snrna. here, we present a comparative analysis of trna(sec) transcription in humans and the parasitic protozoa trypanosoma brucei, two evolutionary highly diverged eukaryotes. rnai-mediated ablation of pol-ii and pol-iii as well as oligo-dt induced transcription termination ... | 2010 | 20444878 |
| anti-trypanosomal effects of aqueous extract of ocimum gratissimum (lamiaceae) leaf in rats infected with trypanosoma brucei brucei. | the anti-trypanosomal effects of aqueous extract of the leaf of ocimum gratissimum were evaluated in both in-vitro and in-vivo studies. the anti-trypanosomal activity of the extract against trypanosoma brucei was investigated in-vitro. the survival and motility of the trypanosomes were completely inhibited within two hours of incubation in various concentrations of the extract. parasite survival time was concentration dependent being longer in lower (25 and 12.5 mg/ml) than higher (100, 75 and 5 ... | 2009 | 20448851 |
| diverse effects on mitochondrial and nuclear functions elicited by drugs and genetic knockdowns in bloodstream stage trypanosoma brucei. | the options for treating the fatal disease human african trypanosomiasis are limited to a few drugs that are toxic or facing increasing resistance. new drugs that kill the causative agents, subspecies of trypanosoma brucei, are therefore urgently needed. little is known about the cellular mechanisms that lead to death of the pathogenic bloodstream stage. | 2010 | 20454560 |
| cell-free synthesis and functional characterization of sphingolipid synthases from parasitic trypanosomatid protozoa. | the trypanosoma brucei genome has four highly similar genes encoding sphingolipid synthases (tbsls1-4). tbslss are polytopic membrane proteins that are essential for viability of the pathogenic bloodstream stage of this human protozoan parasite and, consequently, can be considered as potential drug targets. tbsls4 was shown previously to be a bifunctional sphingomyelin/ethanolamine phosphorylceramide synthase, whereas functions of the others were not characterized. using a recently described lip ... | 2010 | 20457606 |
| resistance and resilience of traditionally managed west african dwarf goats from the savanna zone of northern nigeria to naturally acquired trypanosome and gastrointestinal nematode infections. | a survey was conducted of gastrointestinal nematode infections and trypanosomosis in nigerian west african dwarf (wad) goats from the savanna region of the country. animals were screened at two markets, gboko and akpagher, from the beginning of april until the end of september, coinciding with the end of the dry season and the first 5 months of the wet season. of 1054 goats that were examined, 80.5% carried gastrointestinal (gi) nematodes belonging to the genera haemonchus (61.0%), oesophagostom ... | 2011 | 20459880 |
| functional characterization of two novel parvulins in trypanosoma brucei. | parvulins belong to a family of peptidyl-prolyl cis/trans isomerases (ppiases) that catalyze the cis/trans conformations of prolyl-peptidyl bonds. herein, we characterized two novel parvulins, tbpin1 and tbpar42, in trypanosoma brucei. tbpin1, a 115 amino-acid protein, contains a single ppiase domain but lacks the n-terminal ww domain. using nmr spectroscopy, tbpin1 was found to exhibit ppiase activity toward a phosphorylated substrate. overexpression of tbpin1 can rescue the impaired temperatur ... | 2010 | 20466001 |
| ycf45 protein, usually associated with plastids, is targeted into the mitochondrion of trypanosoma brucei. | ycf45 belongs to a family of proteins of unknown function usually located in the chloroplast of plants. its highly conserved homologues were found in the genomes of several trypanosoma and leishmania species. ha(3)-tagging of the ycf45 protein with the start codon as annotated in the gene(db) revealed its cytosolic localization in the cultured procyclic stage of trypanosoma brucei. however, when a more upstream located start codon was used in another ha(3)-tagged construct, the resulting protein ... | 2010 | 20470834 |
| discrimination of thermophilic and mesophilic proteins. | there is a considerable literature on the source of the thermostability of proteins from thermophilic organisms. understanding the mechanisms for this thermostability would provide insights into proteins generally and permit the design of synthetic hyperstable biocatalysts. | 2010 | 20487512 |
| target of rapamycin (tor)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in trypanosoma brucei. | target of rapamycin (tor) kinases are highly conserved protein kinases that integrate signals from nutrients and growth factors to coordinate cell growth and cell cycle progression. it has been previously described that two tor kinases control cell growth in the protozoan parasite trypanosoma brucei, the causative agent of african trypanosomiasis. here we studied an unusual tor-like protein named tbtor-like 1 containing a pdz domain and found exclusively in kinetoplastids. tbtor-like 1 localizes ... | 2010 | 20495004 |
| partial biochemical characterization of a metalloproteinase from the bloodstream forms of trypanosoma brucei brucei parasites. | metalloproteinases (mmp) belong to the family of cation dependent endopeptidases that degrade matrices at physiological ph and to cleave extracellular matrix proteins. they play an important role in diverse physiological and pathological processes; not only there diverse types of mmp differ in structure and functionally, but also their enzymatic activity is regulated at multiple levels. trying to shed some light over the processes that govern the pathology of african trypanosomiasis, the aim of ... | 2010 | 20496101 |
| molecular diagnostics for sleeping sickness: what is the benefit for the patient? | sleeping sickness, or human african trypanosomiasis, is a vector-borne disease caused by two subspecies of the protozoan parasite trypanosoma brucei, and is geographically restricted to sub-saharan africa. although the disease causes major public-health and socioeconomic problems among affected populations, sleeping sickness is one of the world's most neglected diseases. within the rapidly evolving field of biotechnology, many molecular diagnostics have been developed to detect the parasite. the ... | 2010 | 20510283 |
| new discoveries in the transmission biology of sleeping sickness parasites: applying the basics. | the sleeping sickness parasite, trypanosoma brucei, must differentiate in response to the changing environments that it encounters during its complex life cycle. one developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite. recent advances have shed light on the molecular mechanisms by which these stumpy forms differentiate as they are transmitted from the mammalian host to the insect vector of sleeping sickness, tsetse flie ... | 2010 | 20526573 |
| computer-aided identification of trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for african sleeping sickness. | trypanosoma brucei, the causative agent of human african trypanosomiasis, affects tens of thousands of sub-saharan africans. as current therapeutics are inadequate due to toxic side effects, drug resistance, and limited effectiveness, novel therapies are urgently needed. udp-galactose 4'-epimerase (tbgale), an enzyme of the leloir pathway of galactose metabolism, is one promising t. brucei drug target. we here use the relaxed complex scheme, an advanced computer-docking methodology that accounts ... | 2010 | 20527952 |
| antitrypanosomal alkaloids from polyalthia suaveolens (annonaceae): their effects on three selected glycolytic enzymes of trypanosoma brucei. | in continuation of our study on medicinal plants of cameroon, stem barks of polyalthia suaveolens were phytochemically studied. this investigation yielded a new indolosesquiterpene alkaloid, named polysin (1) and four hitherto known alkaloids (2-5). polysin (1) appeared as a competitive reversible inhibitor (k(i)=10 microm) of phosphofructo kinase (pfk) of trypanosoma brucei with respect to fructose-6-phosphate (k(i)/k(m)=0.05) and could be used in the design of new trypanocidal drugs. the other ... | 2010 | 20529682 |
| trypanosoma brucei modifies the tsetse salivary composition, altering the fly feeding behavior that favors parasite transmission. | tsetse flies are the notorious transmitters of african trypanosomiasis, a disease caused by the trypanosoma parasite that affects humans and livestock on the african continent. metacyclic infection rates in natural tsetse populations with trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. as an obligate blood feeder, tsetse flies rely on ... | 2010 | 20532213 |
| rationally designed squaryldiamides - a novel class of sugar-nucleotide mimics? | sugar-nucleotides such as gdp-mannose, gdp-fucose and udp-glucose are important biomolecules with a central role in carbohydrate and glycoconjugate biosynthesis, metabolism and cell signalling. analogues and mimics of naturally occurring sugar-nucleotides are sought after as chemical tools and inhibitor candidates for sugar-nucleotide-dependent enzymes including glycosyltransferases. many sugar-nucleotides bind to their target glycosyltransferases via coordination of the diphosphate group to a d ... | 2010 | 20532300 |
| assembly of the flagellum and its role in cell morphogenesis in trypanosoma brucei. | eukaryotic flagella are microtubule-based structures required for a variety of functions including cell motility and sensory perception. most eukaryotic flagella grow out from a cell into the surrounding medium, but when the flagellum of the protozoan parasite trypanosoma brucei exits the cell via the flagellar pocket, it is attached along the length of the cell body by a cytoskeletal structure called the flagellum attachment zone (faz). the exact reasons for flagellum attachment have remained e ... | 2010 | 20541452 |
| crystal structures of tbcatb and rhodesain, potential chemotherapeutic targets and major cysteine proteases of trypanosoma brucei. | trypanosoma brucei is the etiological agent of human african trypanosomiasis, an endemic parasitic disease of sub-saharan africa. tbcatb and rhodesain are the sole clan ca papain-like cysteine proteases produced by the parasite during infection of the mammalian host and are implicated in the progression of disease. of considerable interest is the exploration of these two enzymes as targets for cysteine protease inhibitors that are effective against t. brucei. | 2010 | 20544024 |
| trypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in mice. | gene knockout and knockdown methods were used to examine essentiality of pteridine reductase (ptr1) in pterin metabolism in the african trypanosome. attempts to generate ptr1 null mutants in bloodstream form trypanosoma brucei proved unsuccessful; despite integration of drug selectable markers at the target locus, the gene for ptr1 was either retained at the same locus or elsewhere in the genome. however, rna interference (rnai) resulted in complete knockdown of endogenous protein after 48 h, fo ... | 2010 | 20545846 |
| a novel phosphatase cascade regulates differentiation in trypanosoma brucei via a glycosomal signaling pathway. | in the mammalian bloodstream, the sleeping sickness parasite trypanosoma brucei is held poised for transmission by the activity of a tyrosine phosphatase, tbptp1. this prevents differentiation of the transmissible "stumpy forms" until entry into the tsetse fly, whereupon tbptp1 is inactivated and major changes in parasite physiology are initiated to allow colonization of the arthropod vector. using a substrate-trapping approach, we identified the downstream step in this developmental signaling p ... | 2010 | 20551176 |
| 7',8'-dihydroobolactone, a typanocidal alpha-pyrone from the rainforest tree cryptocarya obovata. | mass-directed isolation of the ch(2)cl(2)/meoh extract from the leaves of cryptocarya obovata resulted in the purification of a new trypanocidal alpha-pyrone, 7',8'-dihydroobolactone (1). the chemical structure of 1 was determined by 1d/2d nmr, ms and cd data analysis. 7',8'-dihydroobolactone was shown to inhibit trypanosoma brucei brucei with an ic(50) of 2.8 microm. | 2010 | 20558060 |
| glycotyping of trypanosoma brucei variant surface glycoprotein mitat1.8. | following a switch from variant surface glycoprotein mitat1.4 to variant surface glycoprotein mitat1.8 expression by lister strain 427 trypanosoma brucei brucei parasites, the latter uncharacterized variant surface glycoprotein was analysed. variant surface glycoprotein mitat1.8 was found to be a disulphide-linked homodimer, containing a complex n-linked glycan at asn58 and a glycosylphosphatidylinositol membrane anchor attached to asp419. mass spectrometric analyses demonstrated that the n-glyc ... | 2010 | 20558211 |
| trypanosoma brucei: two steps to spread out from africa. | trypanosoma brucei equiperdum and trypanosoma brucei evansi are typically considered separate species, although a recent study suggested that these organisms can be classified as subspecies of trypanosoma brucei, which we also favor. here we present a scenario that attempts to explain the continuing evolution of the dyskinetoplastic and akinetoplastic strains, as a consequence of loss of selective pressure(s) leading to the loss of kinetoplast dna. | 2010 | 20561822 |
| synthesis of bioactive 2-aza-analogues of ipecac and alangium alkaloids. | | 2010 | 20575140 |
| antiparasitic activity of alkaloids from plant species of papua new guinea and australia. | new drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. in this study, alkaloid compounds isolated from extracts of the plants flindersia amboinensis, stephania zippeliana and voacanga papuana from papua new guinea and flindersia acuminata from australia were examined for their antiparasitic activity against plasmodium falciparum strains and trypanosoma brucei brucei as well as their cytotoxicity agains ... | 2010 | 20580535 |
| cellular and molecular remodeling of the endocytic pathway during differentiation of trypanosoma brucei bloodstream forms. | during the course of mammalian infection, african trypanosomes undergo extensive cellular differentiation, as actively dividing long slender (sl) forms progressively transform into intermediate (i) forms and finally quiescent g(1)/g(0)-locked short stumpy (st) forms. st forms maintain adaptations compatible with their survival in the mammalian bloodstream, such as high endocytic activity, but they already show preadaptations to the insect midgut conditions. the nutritional requirements of st for ... | 2010 | 20581292 |
| in vitro and in vivo anti-trypanosoma brucei activities of phenazinomycin and related compounds. | | 2010 | 20588299 |
| parasites in motion: flagellum-driven cell motility in african trypanosomes. | motility of the sleeping sickness parasite, trypanosoma brucei, impacts disease transmission and pathogenesis. trypanosome motility is driven by a flagellum that harbors a canonical 9+2 axoneme, together with trypanosome-specific elaborations. trypanosome flagellum biology and motility have been the object of intense research over the last two years. these studies have led to the discovery of a novel form of motility, termed social motility, and provided revision of long-standing models for cell ... | 2010 | 20591724 |
| virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase. | the enzyme 6-phosphogluconate dehydrogenase is a potential drug target for the parasitic protozoan trypanosoma brucei, the causative organism of human african trypanosomiasis. this enzyme has a polar active site to accommodate the phosphate, hydroxyl and carboxylate groups of the substrate, 6-phosphogluconate. a virtual fragment screen was undertaken of the enzyme to discover starting points for the development of inhibitors which are likely to have appropriate physicochemical properties for an ... | 2010 | 20598892 |
| dead-box rna helicase is dispensable for mitochondrial translation in trypanosoma brucei. | dead-box rna helicase, a putative subunit of the mitochondrial ribosome of trypanosoma brucei, has been down-regulated in the procyclic and bloodstream stage by rna interference. although ablation of the transcript leads to a week growth phenotype in the procyclic cells, the protein does not seem to be essential for mitochondrial translation under standard cultivation conditions, as shown by an assay that allows visualization of the de novo synthesized proteins. furthermore, we show that synthes ... | 2011 | 20599983 |
| trypanosoma brucei: immunisation with plasmid dna encoding invariant surface glycoprotein gene is able to induce partial protection in experimental african trypanosomiasis. | trypanosoma brucei is the etiological agent responsible for african trypanosomiasis, an infectious pathology which represents a serious problem of public health and economic losses in sub-saharan africa. as one of the foremost neglected illnesses, few resources have been available for the development of vaccines or new drugs, in spite of the current therapeutical drugs showing little efficiency and high toxicity. hence, it is obviously important to widen effective therapeutics and preventive str ... | 2011 | 20599996 |
| small nucleolar rna interference in trypanosoma brucei: mechanism and utilization for elucidating the function of snornas. | expression of dsrna complementary to small nucleolar rnas (snornas) in trypanosoma brucei results in snorna silencing, termed snornai. here, we demonstrate that snornai requires the nuclear tbdcl2 protein, but not tbdcl1, which is involved in rna interference (rnai) in the cytoplasm. snornai depends on argonaute1 (slicer), and on tbdcl2, suggesting that snorna dicing and slicing takes place in the nucleus, and further suggesting that ago1 is active in nuclear silencing. snornai was next utilized ... | 2010 | 20601683 |
| lipidomic analysis of bloodstream and procyclic form trypanosoma brucei. | the biological membranes of trypanosoma brucei contain a complex array of phospholipids that are synthesized de novo from precursors obtained either directly from the host, or as catabolised endocytosed lipids. this paper describes the use of nanoflow electrospray tandem mass spectrometry and high resolution mass spectrometry in both positive and negative ion modes, allowing the identification of approximately 500 individual molecular phospholipids species from total lipid extracts of cultured b ... | 2010 | 20602846 |
| lack of galectin-3 alleviates trypanosomiasis-associated anemia of inflammation. | a typical pathological feature associated with experimental african trypanosomiasis (trypanosoma brucei infection in mice) is anemia of chronic disease (acd), which is due to a sustained type 1 cytokine-mediated inflammation and hyperactivation of m1 macrophages. galectin-3 (gal-3) was amply documented to contribute to the onset and persistence of type 1 inflammatory responses and we herein document that this protein is strongly upregulated during t. brucei infection. we evaluated the involvemen ... | 2010 | 20605052 |
| selective delivery of 2-hydroxy apa to trypanosoma brucei using the melamine motif. | trypanosoma brucei, the parasite that causes human african trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. in particular, the p2 aminopurine transporter can also selectively accumulate melamine derivatives. in this letter, we report the coupling of the melamine moiety to 2-hydroxy apa, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. the best compound described her ... | 2010 | 20615694 |
| the plasma membrane of bloodstream-form african trypanosomes confers susceptibility and specificity to killing by hydrophobic peptides. | trypanosoma brucei is the causative agent of both a veterinary wasting disease and human african trypanosomiasis, or sleeping sickness. the cell membrane of the developmental stage found within the mammalian host, the bloodstream form (bsf), is highly dynamic, exhibiting rapid rates of endocytosis and lateral flow of glycosylphosphatidylinositol-anchored proteins. here, we show that the cell membrane of these organisms is a target for killing by small hydrophobic peptides that increase the rigid ... | 2010 | 20615879 |
| antiprotozoal activity of melampyrum arvense and its metabolites. | an activity guided isolation of the h(2)o subextract of the crude extract of melampyrum arvense l. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8-epi-loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7-o-β-glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9-o-β-glucopyranoside (9); and benzoic acid (10). β-sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the chcl(3) sub ... | 2011 | 20623589 |
| histone deacetylases play distinct roles in telomeric vsg expression site silencing in african trypanosomes. | african trypanosomes evade the host immune response through antigenic variation, which is achieved by periodically expressing different variant surface glycoproteins (vsgs). vsg expression is monoallelic such that only one of approximately 15 telomeric vsg expression sites (ess) is transcribed at a time. epigenetic regulation is involved in vsg control but our understanding of the mechanisms involved remains incomplete. histone deacetylases are potential drug targets for diseases caused by proto ... | 2010 | 20624217 |
| cd200 receptors are differentially expressed and modulated by minocycline in the brain during trypanosoma brucei infection. | infection with trypanosoma brucei, which causes african trypanosomiasis, activates microglia, which are constitutively maintained in a quiescent state through cd200-cd200 receptor interactions. c57bl/6 mice have one inhibitory receptor, cd200r and three activating members, cd200 receptor-like (rl)a-c. infection increased mac-1 (microglia marker), cd200rla and cd200rlb, but not cd200, cd200r or cd200rlc, transcript levels in the brains. minocycline treatment inhibited the infection-induced elevat ... | 2010 | 20627327 |
| topo3alpha influences antigenic variation by monitoring expression-site-associated vsg switching in trypanosoma brucei. | homologous recombination (hr) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (vsg) gene under the control of the active expression site (es). it is believed that the majority of vsg switching events occur by duplicative gene conversion, but only a few dna repair genes that are central to hr have been assigned a role in this process. gene conversion events that are associated with crossover are rarely seen in vsg switchi ... | 2010 | 20628569 |
| a fluorescence-based assay for the uptake of cpd0801 (db829) by african trypanosomes. | drug therapies currently used for second stage human african trypanosomiasis (hat) exhibit problems with toxicity, difficulty of administration, and resistance linked to the loss of transporter function. key to the development of new drugs for hat is a better understanding of the transport properties of candidate compounds. standard methods for studying transport utilize radio-labelled permeant or hplc-ms, however the natural fluorescence of many trypanocidal compounds can be exploited. here we ... | 2010 | 20637807 |
| comparative haematological study of single and mixed infections of mongrel dogs with trypanosoma congolense and trypanosoma brucei brucei. | the haematological effects of single and mixed infections of trypanosoma congolense and trypanosoma brucei brucei were compared in experimentally infected mongrel dogs. twenty mongrel dogs of both sexes aged between 3 and 6 months, and weighing between 2.5 and 5.9 kg were used for the study. the dogs were kept in clean metal cages in a fly-proof house and were adequately fed and given water ad libitum. the twenty dogs were divided into four groups of five dogs each. group i dogs were uninfected ... | 2010 | 20638796 |
| the trypanolytic factor-mechanism, impacts and applications. | the trypanosoma brucei subspecies t. brucei brucei is non-human infective due to susceptibility to lysis by trypanolytic factor (tlf) in human serum. reviewed here are the advances which have revealed apolipoprotein l1 (apol1), found in high density lipoprotein, as the lysis-inducing component of tlf, the means of uptake via haptoglobin-related protein receptor and the mechanism of resistance in t. b. rhodesiense via its serum resistance-associated (sra) protein. the first practical steps to app ... | 2010 | 20646962 |
| genetics. kidney disease is parasite-slaying protein's downside. | | 2010 | 20647431 |
| prophossi: automating expert validation of phosphopeptide-spectrum matches from tandem mass spectrometry. | complex patterns of protein phosphorylation mediate many cellular processes. tandem mass spectrometry (ms/ms) is a powerful tool for identifying these post-translational modifications. in high-throughput experiments, mass spectrometry database search engines, such as mascot provide a ranked list of peptide identifications based on hundreds of thousands of ms/ms spectra obtained in a mass spectrometry experiment. these search results are not in themselves sufficient for confident assignment of ph ... | 2010 | 20651112 |
| the small gtpase arl2 is required for cytokinesis in trypanosoma brucei. | the arf-like (arl) small gtpases have a diverse range of functions in the eukaryotic cell. metazoan arl2 acts as a regulator of microtubule biogenesis, binding to the tubulin-specific chaperone cofactor d. arl2 also has a mitochondrial function through its interactions with bart and ant-1, the only member of the ras superfamily to be found in this organelle to date. in the present study, we describe characterization of the arl2 orthologue in the protozoan parasite trypanosoma brucei. modulation ... | 2010 | 20653091 |
| role of tob55 on mitochondrial protein biogenesis in trypanosoma brucei. | mitochondrial outer membrane (mom) proteins in parasitic protozoa like trypanosoma brucei are poorly characterized. in fungi and higher eukaryotes, tob55 is responsible for the assembly of β-barrel proteins in the mom. here we show that t. brucei tob55 (tbtob55) has considerable similarity in its primary and secondary structure to tob55 from other species. tbtob55 is localized in t. brucei mom and is essential for procyclic cell survival. induction of tob55 rnai decreased the level of the voltag ... | 2010 | 20659504 |
| the trypanosoma brucei mitocarta and its regulation and splicing pattern during development. | it has long been known that trypanosomes regulate mitochondrial biogenesis during the life cycle of the parasite; however, the mitochondrial protein inventory (mitocarta) and its regulation remain unknown. we present a novel computational method for genome-wide prediction of mitochondrial proteins using a support vector machine-based classifier with ∼90% prediction accuracy. using this method, we predicted the mitochondrial localization of 468 proteins with high confidence and have experimentall ... | 2010 | 20660476 |
| discovery of novel orally bioavailable oxaborole 6-carboxamides that demonstrate cure in a murine model of late-stage central nervous system african trypanosomiasis. | we report the discovery of novel boron-containing molecules, exemplified by n-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-trifluoromethylbenzamide (an3520) and 4-fluoro-n-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-trifluoromethylbenzamide (scyx-6759), as potent compounds against trypanosoma brucei in vitro, including the two subspecies responsible for human disease t. b. rhodesiense and t. b. gambiense. these oxaborole carboxamides cured stage 1 (hemolymphatic) trypanosomiasis i ... | 2010 | 20660666 |
| promising lead compounds for novel antiprotozoals. | | 2010 | 20661239 |
| a spectrum of disease in human african trypanosomiasis: the host and parasite genetics of virulence. | for over 50 years it has been known that there are considerable differences in the severity and rate of progression of both trypanosoma brucei rhodesiense and t. b. gambiense infection between individuals. yet research into the factors, whether parasite or host, which control virulence in human african trypanosomiasis is in its infancy. in this paper we review the clinical evidence for virulence variation and the epidemiological and experimental data that give clues as to the mechanisms involved ... | 2010 | 20663245 |
| aryl phosphoramidates of 5-phospho erythronohydroxamic acid, a new class of potent trypanocidal compounds. | rnai and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-pgdh) in trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human african trypanosomiasis. 2,3-o-isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite trypanosoma brucei 6-phosphogluconate dehydrogenase (6-pgdh), the third enzyme of the pentose phosphate pathway. however, this compound does not have trypanocid ... | 2010 | 20666371 |