| In vitro culture of Plasmodium berghei-ANKA maintains infectivity of mouse erythrocytes inducing cerebral malaria. | ABSTRACT: BACKGROUND: Infection with Plasmodium berghei is a widely used model of murine malaria and a powerful tool for reverse genetic and pathogenesis studies. However, the efficacy of in vitro reinvasion of erythrocytes is generally low, limiting in vitro studies. METHODS: Plasmodium berghei ANKA-infected blood obtained from a susceptible infected mouse was cultured in various conditions and in vitro parasitaemia was measured every day to evaluate the rate of reinvasion. RESULTS: High quali ... | 2011 | 22118493 |
| proteolytic breakdown of cytoskeleton induces neurodegeneration during pathology of murine cerebral malaria. | fatal murine cerebral malaria is known to induce cellular degeneration by altering cellular morphology and integrity of cell. the morphology and integrity of the cell mainly depends on the cytoskeletal network of the cell. increased proteolysis of cytoskeletal proteins accompanied by aggravated suicidal proteases activation leads to cellular degeneration. in the present study, we investigated the roles of apoptotic and necrotic cell death proteases, caspase-3, calpain-1 and cathepsin-b in the pr ... | 2011 | 21914552 |
| Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections. | Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita-5,24-diene-3ß,23(R)-diol-7-O-ß-d-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods includi ... | 2011 | 22071523 |
| artemisinin and artemisinin plus curcumin liposomal formulations: enhanced antimalarial efficacy against plasmodium berghei-infected mice. | the therapeutic efficacies of novel liposomal delivery systems based on artemisinin or artemisinin-based combination therapy with curcumin have been investigated and reported in this study. the developed liposomal formulations had proper characteristics as drug carriers for parental administration in terms of particle size, polydispersity, encapsulation efficacy and ζ-potential. their physical and chemical stabilities were also evaluated. furthermore, the in vivo antimalarial activity of artemis ... | 2011 | 22142592 |
| antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives. | a series of new guanidylimidazole derivatives was prepared and evaluated in mice and rhesus monkeys infected with malarial sporozoites. the majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of plasmodium falciparum. compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of p. berghei at 160 and 320 mg/kg/day × 3 po. compounds 8a showed better causal prophylactic activity than primaquine, tafenoquine, and malarone in ... | 2011 | 21848332 |
| characterization and tissue-specific expression patterns of the plasmodium chabaudi cir multigene family. | variant antigens expressed on the surface of parasitized red blood cells (prbcs) are important virulence factors of malaria parasites. whereas plasmodium falciparum erythrocyte membrane proteins 1 (pfemp1) are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other plasmodium species. candidates include members of the pir superfamily found in the human parasite plasmodium vivax (vir), in the simian pathogen plas ... | 2011 | 21929749 |
| Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites. | Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. | 2011 | 21935405 |
| independent roles of apical membrane antigen 1 and rhoptry neck proteins during host cell invasion by apicomplexa. | during invasion, apicomplexan parasites form an intimate circumferential contact with the host cell, the tight junction (tj), through which they actively glide. the tj, which links the parasite motor to the host cell cytoskeleton, is thought to be composed of interacting apical membrane antigen 1 (ama1) and rhoptry neck (ron) proteins. here we find that, in plasmodium berghei, while both ama1 and ron4 are important for merozoite invasion of erythrocytes, only ron4 is required for sporozoite inva ... | 2011 | 22177563 |
| cytofluorometric detection of rodent malaria parasites using red-excited fluorescent dyes. | flow cytometry is a potentially efficient approach for the quantification of parasitemias in experimental malaria infections and drug susceptibility assays using rodent malaria models such as plasmodium berghei. in this study, we used two red dna-binding fluorochromes, rhodamine 800 (r800) and ld700, to measure parasitemia levels in whole blood samples from mice infected with p. berghei. blood samples were treated with rnase a to eliminate rna-derived signals. propidium iodide, which stains both ... | 2011 | 22015734 |
| critical role of the neutrophil-associated high-affinity receptor for ige in the pathogenesis of experimental cerebral malaria. | the role of the ige-fcεri complex in malaria severity in plasmodium falciparum-hosting patients is unknown. we demonstrate that mice genetically deficient for the high-affinity receptor for ige (fcεriα-ko) or for ige (ige-ko) are less susceptible to experimental cerebral malaria (ecm) after infection with plasmodium berghei (pbanka). mast cells and basophils, which are the classical ige-expressing effector cells, are not involved in disease as mast cell-deficient and basophil-depleted mice devel ... | 2011 | 21967768 |
| evaluation of immunity against malaria using luciferase-expressing plasmodium berghei parasites. | abstract: background: measurement of liver stage development is of key interest in malaria biology and vaccine studies. parasite development in liver cells can be visualized in real-time, both in culture and in live mice, using a transgenic plasmodium berghei parasite, pbgfp-luccon, expressing the bioluminescent reporter luciferase. this study explores the benefit of using these parasites for the evaluation of immunity against malaria, compared to qrt-pcr techniques in vivo and in vitro. metho ... | 2011 | 22152047 |
| blood-stage plasmodium berghei infection generates a potent, specific cd8+ t-cell response despite residence largely in cells lacking mhc i processing machinery. | murine cerebral malaria is a complex disease caused by plasmodium berghei anka infection. several cell types, including cd8(+) t cells, are essential effectors of disease. although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic t lymphocytes (ctl) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. our studies show that there is a dramatic p ... | 2011 | 21998471 |
| plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut. | ookinete invasion of the mosquito midgut is an essential step for the development of the malaria parasite in the mosquito. invasion involves recognition between a presumed mosquito midgut receptor and an ookinete ligand. here, we show that enolase lines the ookinete surface. an antienolase antibody inhibits oocyst development of both plasmodium berghei and plasmodium falciparum, suggesting that enolase may act as an invasion ligand. importantly, we demonstrate that surface enolase captures plasm ... | 2011 | 21949403 |
| antiplasmodial activity of xanthium strumarium against plasmodium berghei-infected balb/c mice. | the present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant xanthium strumarium in plasmodium berghei-infected balb/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. the ethanolic leaves extract of x. strumarium (elexs) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with signi ... | 2011 | 21847597 |
| the anti-malarial activity of bivalent imidazolium salts. | a series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of plasmodium falciparum cultures. the activity and selectivity of the compounds for p. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart. the activity of the compounds was not critically dependent on the nature of the linker between the electron-deficient ... | 2011 | 21944972 |
| imaging of plasmodium liver stages to drive next-generation antimalarial drug discovery. | most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. we applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. from this sc ... | 2011 | 22096101 |
| cns hypoxia is more pronounced in murine cerebral than noncerebral malaria and is reversed by erythropoietin. | cerebral malaria (cm) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. to assess the role of cerebral hypoxia, we used two experimental models of cm, plasmodium berghei anka in cba and c57bl/6 mice, and two models of malaria without neurologic signs, p. berghei k173 in cba mice and p. berghei anka in balb/c mice. hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining ... | 2011 | 21854739 |
| reverse fosmidomycin derivatives against the antimalarial drug target ispc (dxr). | reverse hydroxamate-based inhibitors of ispc, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. the binding mode of one derivative in complex with ecispc and a divalent metal ion was clarified by x-ray analysis. pilot experiments have demonstrated in vivo potential. | 2011 | 21866890 |
| expressed sequence tag analysis of the erythrocytic stage of plasmodium berghei. | rodent malaria parasites, such as plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. exploiting the available genetic sequence information, we constructed a cdna library from the erythrocytic stages of p. berghei and analyzed the expressed sequence tag (est). a total of 10,040 ests were generated and assembled into 2,462 clusters. these est clusters were compare ... | 2011 | 22072821 |
| nematode-induced interference with the anti-plasmodium cd8(+) t-cell response can be overcome by optimizing antigen administration. | malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. here we show that strongyloides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against plasmodium berghei. an ongoing infection with litomosoides sigmodontis, a tissue-dwelling filaria that induces chr ... | 2011 | 22161305 |
| Ethnobotanical study of antimalarial plants in Shinile District, Somali Region, Ethiopia, and in vivo evaluation of selected ones against Plasmodium berghei. | The study documented medicinal plants that are traditionally used for treatment of malaria in Shinile District, eastern Ethiopia, and evaluated selected medicinal plants for their antiplasmodial activities against Plasmodium berghei. | 2012 | 22101085 |
| antimalarial activity of physalins b, d, f, and g. | the antimalarial activities of physalins b, d, f, and g (1-4), isolated from physalis angulata, were investigated. in silico analysis using the similarity ensemble approach (sea) database predicted the antimalarial activity of each of these compounds, which were shown using an in vitro assay against plasmodium falciparum. however, treatment of p. berghei-infected mice with 3 increased parasitemia levels and mortality, whereas treatment with 2 was protective, causing a parasitemia reduction and a ... | 2011 | 21954931 |
| erythrocyte remodeling in plasmodium berghei infection: the contribution of sep family members. | the malaria parasite plasmodium largely modifies the infected erythrocyte through the export of proteins to multiple sites within the host cell. this remodeling is crucial for pathology and translocation of virulence factors to the erythrocyte surface. in this study, we investigated localization and export of small exported proteins/early transcribed membrane proteins (sep/etramps), conserved within plasmodium genus. this protein family is characterized by a predicted signal peptide, a short lys ... | 2011 | 22106924 |
| Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT). | A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains were shown to inhibit synthetic hemozoin formation. These compounds were equally active against cultures of chloroquine-sensitive (D10) and chloroquine-resistant (K1) Plasmodium falciparum. The most active compound had an IC(50) value comparable to that of chloroquine, and its potency was undiminished when tested in three additional chloroquine-resistant strains. The three most active compounds exhibited lit ... | 2011 | 21875063 |
| antibody responses to 43 and 48 kda antigens of blood-stage plasmodium berghei in balb/c mice. | progress towards a vaccine against malaria is advancing rapidly with several candidate antigens being tested for their safety and efficacy. in present investigation, two polypeptides (43 and 48 kda) of plasmodium berghei (nk-65) were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. immunogenicity and protective efficacy of both these polypeptides formulated in saponin has been compared in balb/c mice against challenge infection with p. berghei. antibody responses were eva ... | 2010 | 21966123 |
| Antimalaria Effect of the Ethanolic Stem Bark Extracts of Ficus platyphylla Del. | The antimalarial effect of the ethanolic stem bark extract of Ficus platyphylla Del was evaluated against Plasmodium berghei infection in mice. Nontreated, experimental control mice died of fulminant parasitemia from day 7 to 9 post-infection but mice treated with the extract at 300?mg/kg showed markedly reduced parasitaemia bouts of 43.50% and a mean survival time of 28 days postinfection. The plant extract prevented a drastic reduction in PCV showing its efficacy in ameliorating anaemic condit ... | 2011 | 22174991 |
| hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection. | hepcidin is one of the regulators of iron metabolism. the expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. recent studies have indicated that serum hepcidin level is also increased in human subjects infected with plasmodium falciparum. the mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. in this study, we determined the expression of hepcidin in livers of mice infected with plasmodium be ... | 2011 | 22084434 |
| heterogeneous and tissue-specific regulation of effector t cell responses by ifn-gamma during plasmodium berghei anka infection. | ifn-γ and t cells are both required for the development of experimental cerebral malaria during plasmodium berghei anka infection. surprisingly, however, the role of ifn-γ in shaping the effector cd4(+) and cd8(+) t cell response during this infection has not been examined in detail. to address this, we have compared the effector t cell responses in wild-type and ifn-γ(-/-) mice during p. berghei anka infection. the expansion of splenic cd4(+) and cd8(+) t cells during p. berghei anka infection ... | 2011 | 21880980 |
| Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds. | The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC(50) values as low as 60 nM and a certain efficacy in vivo by reduc ... | 2011 | 21940072 |
| Coartemether Induced Oxidative and Hepatic Damage in Plasmodium berghei Strain Anka Infected Mice. | This study investigated the effect of coartemether on antioxidant and hepatotoxic biomarkers in Plasmodium berghei infected mice. Erythrocyte, hepatic and renal superoxide dismutase (2.71 ± 0.51; 1.96 ± 0.87; 2.84 ± 0.22 Units/mg protein respectively) and catalase (4.10 ± 0.10; 8.25 ± 1.24; 6.28 ± 0.11 Units/mg protein respectively) activities were significantly (p < 0.05) elevated in "parasitized and treated" (PnT) animals. Renal glutathione level (19.02 ± 0.20 µg/mL) was elevated in PnT animal ... | 2011 | 22057281 |
| high-throughput multi-parameter flow-cytometric analysis from micro-quantities of plasmodium-infected blood. | despite significant technological and conceptual advances over the last century, evaluation of the efficacy of anti-malarial vaccines or drugs continues to rely principally on direct microscopic visualisation of parasites on thick and/or thin giemsa-stained blood smears. this requires technical expertise of the microscopist, is highly subjective and error-prone, and does not account for aberrations such as anaemia. many published methods have shown that flow cytometric analysis of blood is a hig ... | 2011 | 21907206 |
| experimental cerebral malaria develops independently of card9 signalling. | the outcome of infection depends on multiple layers of immune regulation with innate immunity playing a decisive role in shaping protection or pathogenic sequelae of acquired immunity. the contribution of pattern recognition receptors and adaptor molecules in immunity to malaria remains poorly understood. here we interrogate the role of the caspase recruitment domain-containing protein 9 (card9) signalling pathway in the development of experimental cerebral malaria (ecm) using the murine plasmod ... | 2011 | 22158744 |
| FLP/FRT-mediated conditional mutagenesis in pre-erythrocytic stages of Plasmodium berghei. | We describe here a highly efficient procedure for conditional mutagenesis in Plasmodium. The procedure uses the site-specific recombination FLP-FRT system of yeast and targets the pre-erythrocytic stages of the rodent Plasmodium parasite P. berghei, including the sporozoite stage and the subsequent liver stage. The technique consists of replacing the gene under study by an FRTed copy (i.e., flanked by FRT sites) in the erythrocytic stages of a parasite clone that expresses the flip (FLP) recombi ... | 2011 | 21886105 |
| A carbamate-based approach to primaquine prodrugs: Antimalarial activity, chemical stability and enzymatic activation. | O-Alkyl and O-aryl carbamate derivatives of the antimalarial drug primaquine were synthesised as potential prodrugs that prevent oxidative deamination to the inactive metabolite carboxyprimaquine. Both O-alkyl and O-aryl carbamates undergo hydrolysis in alkaline and pH 7.4 phosphate buffers to the parent drug, with O-aryl carbamates being ca. 10(6)-10(10) more reactive than their O-alkyl counterparts. In human plasma O-alkyl carbamates were stable, whereas in contrast their O-aryl counterparts r ... | 2011 | 22189276 |
| inactivation of a plasmodium apicoplast protein attenuates formation of liver merozoites. | malaria parasites undergo a population expansion inside the host liver before disease onset. developmental arrest inside host hepatocytes elicits protective immune responses. therefore, elucidation of the molecular mechanisms leading to mature hepatic merozoites, which initiate the pathogenic blood phase, also informs anti-malaria vaccine strategies. using targeted gene deletion in the rodent model malaria parasite plasmodium berghei, we show that a plasmodium-specific apicoplast protein plays a ... | 2011 | 21848587 |
| nogo-a expression in the brain of mice with cerebral malaria. | cerebral malaria (cm) is associated with a high rate of transient or persistent neurological sequelae. nogo-a, a protein that is highly expressed in the endoplasmic reticulum (er) of the mammalian central nervous system (cns), is involved in neuronal regeneration and synaptic plasticity in the injured cns. the current study investigates the role of nogo-a in the course of experimental cm. c57bl/6j mice were infected with plasmodium berghei anka blood stages. brain homogenates of mice with differ ... | 2011 | 21980529 |
| a gfp-actin reporter line to explore microfilament dynamics across the malaria parasite lifecycle. | malaria parasite motility relies on an internal parasite actomyosin motor that, when linked to the host cell substrate, propels motile zoites forward. despite their key role in this process, attempts to visualize actin microfilaments (f-actin) during motility and under native microscopy conditions have not to date been successful. towards facilitating their visualization we present here a plasmodium berghei transgenic line in which a green fluorescent protein (gfp)-actin fusion is constitutively ... | 2011 | 22138565 |
| structure-activity relationships of 4-position diamine quinoline methanols as intermittent preventative treatment (ipt) against plasmodium falciparum. | a library of diamine quinoline methanols were designed based on the mefloquine scaffold. the systematic variation of the 4-position amino alcohol side chain led to analogues that maintained potency while reducing accumulation in the central nervous system (cns). although the mechanism of action remains elusive, these data indicate that the 4-position side chain is critical for activity and that potency (as measured by ic(90)) does not correlate with accumulation in the cns. a new lead compound, ... | 2011 | 21854078 |
| Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives. | Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cy ... | 2011 | 21924377 |
| quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria. | the pathogenic mechanisms underlying the occurrence of cerebral malaria (cm) are still incompletely understood but, clearly, cerebral complications may result from concomitant microvessel obstruction and inflammation. the extent to which brain edema contributes to pathology has not been investigated. using the model of p. berghei anka infection, we compared brain microvessel morphology of cm-susceptible and cm-resistant mice. by quantitative planimetry, we provide evidence that cm is characteriz ... | 2011 | 21904632 |
| reduced cd36-dependent tissue sequestration of plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. | adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of plasmodium falciparum malaria. the prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. irbc of the rodent parasite plasmodium berghei anka sequester in a fashion analogous to p. falciparum by adhering to the host receptor cd36. to experimentally determine the significance of seques ... | 2011 | 22184632 |
| il-12rβ2 is essential for the development of experimental cerebral malaria. | a th1 response is required for the development of plasmodium berghei anka (pba)-induced experimental cerebral malaria (ecm). the role of pro-th1 il-12 in malaria is complex and controversial. in this study, we addressed the role of il-12rβ2 in ecm development. c57bl/6 mice deficient for il-12rβ2, il-12p40, or il-12p35 were analyzed for ecm development after blood-stage pba infection in terms of ischemia and blood flow by noninvasive magnetic resonance imaging and angiography, t cell recruitment, ... | 2012 | 22238458 |
| highly dynamic host actin reorganization around developing plasmodium inside hepatocytes. | plasmodium sporozoites are transmitted by anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. the nature of the plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. here we show that highly dynamic hepatocyte actin reorganization events occur around developing plasmodium berghei parasites inside human hepatoma cells. actin reorganizat ... | 2012 | 22238609 |
| testing in mice the hypothesis that melanin is protective in malaria infections. | malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. modern humans originated in africa and lost skin melanization as they migrated to temperate regions of the globe. although it is well documented that loss of melanization improved cutaneous vitamin d synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melani ... | 2012 | 22242171 |
| sem studies on blood cells of plasmodium berghei infected balb/c mice treated with artesunate and homeopathic medicine china. | the therapeutic efficacy of antimalarial drugs and their effect on various organs in the form of surface morphological deformations can be analyzed using scanning electron microscopy (sem). present study has been undertaken on plasmodium berghei (nk-65), a lethal rodent malaria parasite, to monitor the morphological changes in blood cells induced by the treatment with combination of artesunate and homeopathic medicine . combination therapy of artesunate (100 mg/kg) and china ϕ was found to be hi ... | 2011 | 23024494 |
| histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult wistar rats. | lamivudine and artesunate are sometimes co administered in hiv-malaria co morbidity. both drugs are used concurrently in presumptive malaria treatment and simultaneous hiv post exposure prophylaxis. | 2011 | 22540106 |
| disruption of plasmepsin-4 and merozoites surface protein-7 genes in plasmodium berghei induces combined virulence-attenuated phenotype. | blood stage malaria parasites causing a mild and self limited infection in mice have been obtained with either radiation or chemical mutagenesis showing the possibility of developing an attenuated malaria vaccine. targeted disruption of plasmepsin-4 (pm4) or the merozoite surface protein-7 (msp7) genes also induces a virulence-attenuated phenotype in terms of absence of experimental cerebral malaria (ecm), delayed increase of parasitemia and reduced mortality rate. the decrease in virulence in p ... | 2011 | 22355558 |
| genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease. | genes underlying important phenotypic differences between plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. we hypothesized that chromosome-internal regions of plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. we combined sequence similarity searches wi ... | 2011 | 22215999 |
| malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential. | plasmodium falciparum (p. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. the global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. we identified the carbonic anhydrase (ca) genes in p. falciparum. the pfca gene encodes anα-carbonic anhydrase, a zn(2+)-metalloenzme, possessing catalytic properties distinct from that o ... | 2011 | 23569766 |
| [antimalarial activity of hydroalcoholic extract from bixa orellana l]. | bixa orellana l. is one species used in traditional herb medicine in several continents. among the medicinal properties attributed to this plant, the antimalarial action has been included. | 2011 | 23437529 |
| effects of low protein diet and pregnancy on course of plasmodium berghei infection in mice. | pregnancy and malnutrition influence the severity or trend of malaria especially in sub-saharan africa where parasitic infections are highly predominant. this study was used to evaluate the combined effects of low protein diet and pregnancy on the course of plasmodium berghei infection in mice. thirty female balb/c mice were divided into six groups viz: non-infected mice fed on normal diet (nind), infected mice fed on normal diet (ind), noninfected mice fed on low protein diet (nilp), infected m ... | 2012 | 23678649 |
| therapeutic effects of various solvent fractions of alstonia boonei (apocynaceae) stem bark on plasmodium berghei-induced malaria. | malaria, the most important parasitic disease afflicting man is the leading cause of mortality and morbidity in the world. chemotherapy remains the mainstay for the treatment and prevention of the disease in the absence of an effective vaccine. the incidence of resistance of malaria parasites to chemotherapy is increasing and complicated. this study was therefore undertaken in order to evaluate the therapeutic effects of fractions of the stem bark of a. boonei on p. berghei-induced malaria using ... | 2012 | 23678633 |
| comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis. | to evaluate the effects of quinine and chloroquine against male mice infected with plasmodium berghei and their adverse effects on the mice testes. | 2012 | 23569921 |
| [application of flow cytometry in the detection of mouse malaria parasites in living cells]. | peripheral blood samples were obtained from plasmodium berghei-infected mice, and stained with vybrant dyecycle green and anti-mouse cd71 pe. with normal mouse as negative control, the blood samples were tested by flow cytometry at 0, 30, and 60 min after staining. there was no positive signal in the erythrocytes from negative control and the unstained erythrocytes from the infected mouse. however, the positive signal was detected in the stained erythrocytes from the infected mouse. the results ... | 2012 | 23484270 |
| antiplasmodial potential of the african mistletoe: agelanthus dodoneifolius polh and wiens. | preparations of agelanthus dodoneifolius have been used in the traditional nigerian medicine to treat malaria and this practice has remained till date without scientific validation. the antiplasmodial property of the water extract of agelanthus dodoneifolius was evaluated in vivo and in vitro against plasmodium berghei and clinical isolates of plasmodium falciparum, respectively. there was a dose-dependent inhibition of parasitaemia in the in vivo antiplasmodial tests likewise, the in vitro scre ... | 2012 | 23441021 |
| [in vivo antiplasmodial activity of mycale laxissima and clathria echinata sponges]. | the search of new antimalarial compounds comprises, among its challenges, the development of therapeutic alternatives for cerebral malaria; due to the high mortality and neurological deficiencies that persist after treatment with recommended drugs. | 2012 | 23424801 |
| efficacy of eosin b as a new antimalarial drug in a murine model. | the initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. the search for new drugs and drug targets is a consistent demand in this disease. eosin b, a common laboratory dye, is reported to have good antiparasitic properties in vitro. it was studied for its antiparasitic effect in vivo on chloroquine-sensitive plasmodium berghei murine malaria. eosin b was administered in 2 different doses by either the oral or parente ... | 2012 | 23365788 |
| plasmodium berghei anka infection in icr mice as a model of cerebral malaria. | animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. here, we describe the combination of plasmodium berghei anka infection in inbred icr mice as a model of cerebral malaria (cm). | 2012 | 23323093 |
| statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. | cerebral malaria (cm) is the most severe manifestation of plasmodium falciparum infection in children and non-immune adults. previous work has documented a persistent cognitive impairment in children who survive an episode of cm that is mimicked in animal models of the disease. potential therapeutic interventions for this complication have not been investigated, and are urgently needed. hmg-coa reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. in addition to their ... | 2012 | 23300448 |
| aberrant sporogonic development of dmc1 (a meiotic recombinase) deficient plasmodium berghei parasites. | in plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. | 2012 | 23285059 |
| protective role of brain water channel aqp4 in murine cerebral malaria. | tragically common among children in sub-saharan africa, cerebral malaria is characterized by rapid progression to coma and death. in this study, we used a model of cerebral malaria appearing in c57bl/6 wt mice after infection with the rodent malaria parasite plasmodium berghei anka. expression and cellular localization of the brain water channel aquaporin-4 (aqp4) was investigated during the neurological syndrome. semiquantitative real-time pcr comparing uninfected and infected mice showed a red ... | 2012 | 23277579 |
| full-length plasmodium falciparum circumsporozoite protein administered with long-chain poly(i·c) or the toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and cd4+ t cell immunity and protection in mice. | the plasmodium falciparum circumsporozoite (cs) protein (csp) is a major vaccine target for preventing malaria infection. thus, developing strong and durable antibody and t cell responses against csp with novel immunogens and potent adjuvants may improve upon the success of current approaches. here, we compare four distinct full-length p. falciparum cs proteins expressed in escherichia coli or pichia pastoris for their ability to induce immunity and protection in mice when administered with long ... | 2012 | 23275094 |
| csp--a model for in vivo presentation of plasmodium berghei sporozoite antigens by hepatocytes. | one target of protective immunity against the plasmodium liver stage in balb/c mice is represented by the circumsporozoite protein (csp), and mainly involves its recognition by ifn-γ producing specific cd8+t-cells. in a previous in vitro study we showed that primary hepatocytes from balb/c mice process plasmodium berghei (pb) csp (pbcsp) and present csp-derived peptides to specific h-2k(d) restricted cd8+t-cells with subsequent killing of the presenting cells. we now extend these observations to ... | 2012 | 23272182 |
| visualizing non infectious and infectious anopheles gambiae blood feedings in naive and saliva-immunized mice. | anopheles gambiae is a major vector of malaria and lymphatic filariasis. the arthropod-host interactions occurring at the skin interface are complex and dynamic. we used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding. | 2012 | 23272060 |
| mosquito akirin as a potential antigen for malaria control. | the control of vector-borne diseases is important to improve human and animal health worldwide. malaria is one of the world's deadliest diseases and is caused by protozoan parasites of the genus plasmodium, which are transmitted by anopheles spp. mosquitoes. recent evidences using subolesin (sub) and akirin (akr) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. these experiments suggested the possibi ... | 2014 | 25472895 |
| antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens. | microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. a β-(1→6)-linked poly-n-acetyl-d-glucosamine (pnag) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in staphylococcus aureus or polyglucosamine in selected gram-negative bacterial pathogens. we report that many microbial pathogens lacking an identifiable intercellular adhe ... | 2013 | 23716675 |
| antimalarial activity of the myxobacterial macrolide chlorotonil a. | myxobacteria are gram-negative soil-dwelling bacteria belonging to the phylum proteobacteria. they are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. in the course of a bioactivity screening program of secondary metabolites produced by sorangium cellulosum strains, the macrolide chlorotonil a was found to exhibit promising antimalarial activity. subsequently, we evaluated chlorotonil a against plasmodium falcipar ... | 2014 | 25114138 |
| erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia. | malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. we examined the regulation of hepcidin during malarial infection in mice using the rodent parasite plasmodium berghei k173. mice infected with plasmodium berghei k173 develop a severe anemia and die after 18 to 22 ... | 2017 | 27658439 |
| a yeast strain associated to anopheles mosquitoes produces a toxin able to kill malaria parasites. | malaria control strategies are focusing on new approaches, such as the symbiotic control, which consists in the use of microbial symbionts to prevent parasite development in the mosquito gut and to block the transmission of the infection to humans. several microbes, bacteria and fungi, have been proposed for malaria or other mosquito-borne diseases control strategies. among these, the yeast wickerhamomyces anomalus has been recently isolated from the gut of anopheles mosquitoes, where it release ... | 2016 | 26754943 |
| a nondiscriminating glutamyl-trna synthetase in the plasmodium apicoplast: the first enzyme in an indirect aminoacylation pathway. | the malaria parasite plasmodium falciparum and related organisms possess a relict plastid known as the apicoplast. apicoplast protein synthesis is a validated drug target in malaria because antibiotics that inhibit translation in prokaryotes also inhibit apicoplast protein synthesis and are sometimes used for malaria prophylaxis or treatment. we identified components of an indirect aminoacylation pathway for gln-trna(gln) biosynthesis in plasmodium that we hypothesized would be essential for api ... | 2013 | 24072705 |
| plasmodium apicoplast gln-trnagln biosynthesis utilizes a unique gatab amidotransferase essential for erythrocytic stage parasites. | the malaria parasite plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-trna synthetase to synthesize glu-trna(gln) and a glutaminyl-trna amidotransferase to convert glu-trna(gln) to gln-trna(gln). here, we show that plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyl-trna amidotransferase consisting of gata and gatb subunits (gatab). we localized the p. falciparum gata and gatb subunits to the apicoplast in b ... | 2015 | 26318454 |
| bckdh: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of toxoplasma gondii and plasmodium berghei. | while the apicomplexan parasites plasmodium falciparum and toxoplasma gondii are thought to primarily depend on glycolysis for atp synthesis, recent studies have shown that they can fully catabolize glucose in a canonical tca cycle. however, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-coa remains enigmatic. here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase ... | 2014 | 25032958 |
| functional genomic analyses of enterobacter, anopheles and plasmodium reciprocal interactions that impact vector competence. | malaria exerts a tremendous socioeconomic impact worldwide despite current control efforts, and novel disease transmission-blocking strategies are urgently needed. the enterobacter bacterium esp_z, which is naturally harboured in the mosquito midgut, can inhibit the development of plasmodium parasites prior to their invasion of the midgut epithelium through a mechanism that involves oxidative stress. here, a multifaceted approach is used to study the tripartite interactions between the mosquito, ... | 2016 | 27549662 |
| experimental genetics of plasmodium berghei nfu in the apicoplast iron-sulfur cluster biogenesis pathway. | eukaryotic pathogens of the phylum apicomplexa contain a non-photosynthetic plastid, termed apicoplast. within this organelle distinct iron-sulfur [fe-s] cluster proteins are likely central to biosynthesis pathways, including generation of isoprenoids and lipoic acid. here, we targeted a nuclear-encoded component of the apicoplast [fe-s] cluster biosynthesis pathway by experimental genetics in the murine malaria parasite plasmodium berghei. we show that ablation of the gene encoding a nitrogen f ... | 2013 | 23805304 |
| detection of viable plasmodium ookinetes in the midguts of anopheles coluzzi using pma-qrtpcr. | mosquito infection with malaria parasites depends on complex interactions between the mosquito immune response, the parasite developmental program and the midgut microbiota. simultaneous monitoring of the parasite and bacterial dynamics is important when studying these interactions. pcr based methods of genomic dna (gdna) have been widely used, but their inability to discriminate between live and dead cells compromises their application. the alternative method of quantification of mrna mainly re ... | 2015 | 26373633 |
| chemobiosynthesis of new antimalarial macrolides. | we have synthesized new derivatives of the macrolide antibiotics erythromycin and azithromycin. novel deoxysugar moieties were attached to these standard antibiotics by biotransformation using a heterologous host. the resulting compounds were tested against several standard laboratory and clinically isolated bacterial strains. in addition, they were also tested in vitro against standard and drug-resistant strains of human malaria parasites (plasmodium falciparum) and the liver stages of the rode ... | 2013 | 23208707 |
| generation of rodent malaria parasites with a high mutation rate by destructing proofreading activity of dna polymerase δ. | plasmodium falciparum malaria imposes a serious public health concern throughout the tropics. although genetic tools are principally important to fully investigate malaria parasites, currently available forward and reverse tools are fairly limited. it is expected that parasites with a high mutation rate can readily acquire novel phenotypes/traits; however, they remain an untapped tool for malaria biology. here, we generated a mutator malaria parasite (hereinafter called a 'malaria mutator'), usi ... | 2014 | 24670267 |
| plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice. | the design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge. | 2014 | 25373617 |
| depletion of regulatory t cells augments a vaccine-induced t effector cell response against the liver-stage of malaria but fails to increase memory. | regulatory t cells (t(reg)) have been shown to restrict vaccine-induced t cell responses in different experimental models. in these studies cd4(+)cd25(+) t(reg) were depleted using monoclonal antibodies against cd25, which might also interfere with cd25 on non-regulatory t cell populations and would have no effect on foxp3(+)cd25(-) t(reg). to obtain more insights in the specific function of t(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressi ... | 2014 | 25115805 |
| fighting malaria with engineered symbiotic bacteria from vector mosquitoes. | the most vulnerable stages of plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. the escherichia coli hemolysin a secretion system was used to promote the secretion of a variety of anti-plasmodium effector proteins by pantoea agglomerans, a common mosqui ... | 2012 | 22802646 |
| multiple pathways for plasmodium ookinete invasion of the mosquito midgut. | plasmodium ookinete invasion of the mosquito midgut is a crucial step of the parasite life cycle but little is known about the molecular mechanisms involved. previously, a phage display peptide library screen identified sm1, a peptide that binds to the mosquito midgut epithelium and inhibits ookinete invasion. sm1 was characterized as a mimotope of an ookinete surface enolase and sm1 presumably competes with enolase, the presumed ligand, for binding to a putative midgut receptor. here we identif ... | 2014 | 24474798 |
| inhibition of plasmodium berghei development in mosquitoes by effector proteins secreted from asaia sp. bacteria using a novel native secretion signal. | novel interventions are needed to prevent the transmission of the plasmodium parasites that cause malaria. one possible method is to supply mosquitoes with antiplasmodial effector proteins from bacteria by paratransgenesis. mosquitoes have a diverse complement of midgut microbiota including the gram-negative bacteria asaia bogorensis. this study presents the first use of asaia sp. bacteria for paratransgenesis against p. berghei. we identified putative secreted proteins from a. bogorensis by a g ... | 2015 | 26636338 |
| enterobacter-activated mosquito immune responses to plasmodium involve activation of srpn6 in anopheles stephensi. | successful development of plasmodium in the mosquito is essential for the transmission of malaria. a major bottleneck in parasite numbers occurs during midgut invasion, partly as a consequence of the complex interactions between the endogenous microbiota and the mosquito immune response. we previously identified srpn6 as an immune component which restricts plasmodium berghei development in the mosquito. here we demonstrate that srpn6 is differentially activated by bacteria in anopheles stephensi ... | 2013 | 23658788 |
| identification of vital and dispensable sulfur utilization factors in the plasmodium apicoplast. | iron-sulfur [fe-s] clusters are ubiquitous and critical cofactors in diverse biochemical processes. they are assembled by distinct [fe-s] cluster biosynthesis pathways, typically in organelles of endosymbiotic origin. apicomplexan parasites, including plasmodium, the causative agent of malaria, harbor two separate [fe-s] cluster biosynthesis pathways in the their mitochondrion and apicoplast. in this study, we systematically targeted the five nuclear-encoded sulfur utilization factors (suf) of t ... | 2014 | 24586983 |
| malaria infection does not affect the sensitivity of peripheral receptor neurons in anopheles stephensi. | mosquitoes transmit many important diseases including malaria, dengue and yellow fever. disease transmission from one vertebrate host to another depends on repeated blood feedings by single mosquitoes. in order for the mosquito to acquire the blood that it needs to complete oogenesis, the insect must locate a suitable host. olfactory cues (including carbon dioxide) released by the host and detected by the mosquito are the primary signals that vector insects use for host location. previous studie ... | 2013 | 23642231 |
| anopheles gambiae antiviral immune response to systemic o'nyong-nyong infection. | mosquito-borne viral diseases cause significant burden in much of the developing world. although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. in contrast to mosquitoes of the aedes and culex genera, anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is o'nyong-nyong virus (onnv). here we have investigated the a. gambiae immune ... | 2012 | 22428080 |
| plasmodium berghei sporozoites acquire virulence and immunogenicity during mosquito hemocoel transit. | malaria is a vector-borne disease caused by the single-cell eukaryote plasmodium. the infectious parasite forms are sporozoites, which originate from midgut-associated oocysts, where they eventually egress and reach the mosquito hemocoel. sporozoites actively colonize the salivary glands in order to be transmitted to the mammalian host. whether residence in the salivary glands provides distinct and vital cues for the development of infectivity remains unsolved. in this study, we systematically c ... | 2013 | 24379288 |
| gene expression changes in the salivary glands of anopheles coluzzii elicited by plasmodium berghei infection. | malaria is a devastating infectious disease caused by plasmodium parasites transmitted through the bites of infected anopheles mosquitoes. salivary glands are the only mosquito tissue invaded by plasmodium sporozoites, being a key stage for the effective parasite transmission, making the study of anopheles sialome highly relevant. | 2015 | 26395987 |
| exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage plasmodium berghei infection. | the thymus plays an important role shaping the t cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. it has been shown that, during plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of cd4+cd8+ double-positive (dp) t cells to the periphery. to investigate whether autoimmune diseases are affected after plasmodium berghei nk65 infection, we immunized c57bl/6 mice, which was previously infected with p. berghei nk ... | 2014 | 25329161 |
| immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates plasmodium infection in mice. | subtilisin-like protease 2 (sub2) is a conserved serine protease utilized by plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. to determine if sub2 is a suitable vaccine target to interfere with malaria parasite development, the effects of sub2-immunization on the plasmodium life cycle were examined in its vertebrate and invertebrate hosts. | 2014 | 25115675 |
| the utility of plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment. | rodent malaria species plasmodium yoelii and p. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. however, increasing data suggest the p. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. here we confirm a failure to protect against p. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. no subunit vaccine approa ... | 0 | 23609325 |
| maldi-tof ms as an innovative tool for detection of plasmodium parasites in anopheles mosquitoes. | malaria is still a major public health issue worldwide, and one of the best approaches to fight the disease remains vector control. the current methods for mosquito identification include morphological methods that are generally time-consuming and require expertise, and molecular methods that require laboratory facilities with relatively expensive running costs. matrix-assisted laser desorption ionization time-of-flight mass spectrometry (maldi-tof ms) technology, routinely used for bacterial id ... | 2017 | 28049524 |
| phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito. | the blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. the proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. to better understand this process we generated a global profile of metabolite changes in response to blood meal of anopheles gambiae, using gas chromatography-mass spectrometry (gc-ms). to disrupt a key pathway ... | 2014 | 24409310 |
| an overview of malaria transmission from the perspective of amazon anopheles vectors. | in the americas, areas with a high risk of malaria transmission are mainly located in the amazon forest, which extends across nine countries. one keystone step to understanding the plasmodium life cycle in anopheles species from the amazon region is to obtain experimentally infected mosquito vectors. several attempts to colonise anopheles species have been conducted, but with only short-lived success or no success at all. in this review, we review the literature on malaria transmission from the ... | 2015 | 25742262 |
| an epithelial serine protease, agesp, is required for plasmodium invasion in the mosquito anopheles gambiae. | plasmodium parasites need to cross the midgut and salivary gland epithelia to complete their life cycle in the mosquito. however, our understanding of the molecular mechanism and the mosquito genes that participate in this process is still very limited. | 2012 | 22509400 |
| plasmodium transmission blocking activities of vernonia amygdalina extracts and isolated compounds. | medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. the aim of this study was to assess the activity of vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of plasmodium berghei and to validate the findings on field isolates of plasmodium falciparum. | 2015 | 26208861 |
| discovery of hdac inhibitors with potent activity against multiple malaria parasite life cycle stages. | in this work we investigated the antiplasmodial activity of a series of hdac inhibitors containing an alkoxyamide connecting-unit linker region. hdac inhibitor 1a (lmk235), previously shown to be a novel and specific inhibitor of human hdac4 and 5, was used as a starting point to rapidly construct a mini-library of hdac inhibitors using a straightforward solid-phase supported synthesis. several of these novel hdac inhibitors were found to have potent in vitro activity against asexual stage plasm ... | 2014 | 24904967 |
| cd8+ t cells from a novel t cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria. | to follow the fate of cd8+ t cells responsive to plasmodium berghei anka (pba) infection, we generated an mhc i-restricted tcr transgenic mouse line against this pathogen. t cells from this line, termed pbt-i t cells, were able to respond to blood-stage infection by pba and two other rodent malaria species, p. yoelii xnl and p. chabaudi as. these pbt-i t cells were also able to respond to sporozoites and to protect mice from liver-stage infection. examination of the requirements for priming afte ... | 2014 | 24854165 |
| development of a transgenic plasmodium berghei line (pb pfpkg) expressing the p. falciparum cgmp-dependent protein kinase, a novel antimalarial drug target. | with the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. in this study we set out to develop a transgenic rodent model for testing inhibitors of the plasmodium falciparum cyclic gmp-dependent kinase in vivo. a model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences i ... | 2014 | 24805991 |
| a rapid and robust selection procedure for generating drug-selectable marker-free recombinant malaria parasites. | experimental genetics have been widely used to explore the biology of the malaria parasites. the rodent parasites plasmodium berghei and less frequently p. yoelii are commonly utilised, as their complete life cycle can be reproduced in the laboratory and because they are genetically tractable via homologous recombination. however, due to the limited number of drug-selectable markers, multiple modifications of the parasite genome are difficult to achieve and require large numbers of mice. here we ... | 2014 | 24755823 |