Publications

endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria.	we hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. c57bl/6 mice were infected with plasmodium berghei anka, resulting in cerebral malaria, or p. chabaudi as, resulting in uncomplicated malaria. we visualized the glycocalyx with transmission electron microscopy and measured circulating glycosaminoglycans by dot blot and elisa. the glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. it was ...	2014	24756075
mice rescued from severe malaria are protected against renal injury during a second kidney insult.	malaria is a worldwide disease that leads to 1 million deaths per year. plasmodium falciparum is the species responsible for the most severe form of malaria leading to different complications. beyond the development of cerebral malaria, impairment of renal function is a mortality indicator in infected patients. treatment with antimalarial drugs can increase survival, however the long-term effects of malaria on renal disease, even after treatment with antimalarials, are unknown. the aim of this s ...	2014	24736406
repositioning: the fast track to new anti-malarial medicines?	repositioning of existing drugs has been suggested as a fast track for developing new anti-malarial agents. the compound libraries of glaxosmithkline (gsk), pfizer and astrazeneca (az) comprising drugs that have undergone clinical studies in other therapeutic areas, but not achieved approval, and a set of us food and drug administration (fda)-approved drugs and other bio-actives were tested against plasmodium falciparum blood stages.	2014	24731288
anti-malarial activity of indole alkaloids isolated from aspidosperma olivaceum.	several species of aspidosperma (apocynaceae) are used as treatments for human diseases in the tropics. aspidosperma olivaceum, which is used to treat fevers in some regions of brazil, contains the monoterpenoid indole alkaloids (mias) aspidoscarpine, uleine, apparicine, and n-methyl-tetrahydrolivacine. using bio-guided fractionation and cytotoxicity testing in a human hepatoma cell line, several plant fractions and compounds purified from the bark and leaves of the plant were characterized for ...	2014	24731256
in vitro and in vivo antiplasmodial activity of three rwandan medicinal plants and identification of their active compounds.	in our previous study, we reported the interesting in vitro antiplasmodial activity of some rwandan plant extracts. this gave rise to the need for these extracts to also be evaluated in vivo and to identify the compounds responsible for their antiplasmodial activity. the aim of our study was, on the one hand, to evaluate the antiplasmodial activity in vivo and the safety of the selected rwandan medicinal plants used in the treatment of malaria, with the objective of promoting the development of ...	2014	24710900
memory t cells maintain protracted protection against malaria.	immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. adequately maintained memory t and b cell pools assure a fast, effective and specific response against re-infections. however, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, plasmodium spp., the causative agents of malar ...	2014	24709142
cross-talk between malarial cysteine proteases and falstatin: the bc loop as a hot-spot target.	cysteine proteases play a crucial role in the development of the human malaria parasites plasmodium falciparum and plasmodium vivax. our earlier studies demonstrated that these enzymes are equipped with specific domains for defined functions and further suggested the mechanism of activation of cysteine proteases. the activities of these proteases are regulated by a new class of endogenous inhibitors of cysteine proteases (icps). structural studies of the icps of trypanosoma cruzi (chagasin) and ...	2014	24699522
quantitative analysis of cepharanthine in plasma based on semiautomatic microextraction by packed sorbent combined with liquid chromatography.	the spread of plasmodium falciparum resistance toward most of the used drugs requires new antimalarial compounds. taking advantage of the biodiversity, the ethnopharmacological approach opens the way for the discovery and the characterization of potent original molecules. previous works led to the selection of a bisbenzylisoquinoline, cepharanthine, extracted from stephania rotunda, which is mainly present in cambodia. a sensitive and selective liquid chromatography method has been developed for ...	2014	24693462
d-glucose concentration is the key factor facilitating liver stage maturation of plasmodium.	the course of malaria infection in mammals begins with transmission of plasmodium sporozoites into the skin by anopheles mosquitoes, followed by migration of the sporozoites to the liver. as no symptoms present until hepatic merozoites are released and until they infect erythrocytes in the blood vessels, sporozoites and liver-stage (ls) parasites are promising targets for anti-malaria drugs aiming to prevent mosquito-to-mammal transmission. in vitro ls parasite development system is useful in th ...	2014	24691399
dendritic cells treated with crude plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.	dendritic cells (dcs) are professional antigen-presenting cells specifically targeted during plasmodium infection. upon infection, dcs show impaired antigen presentation and t-cell activation abilities. in this study, we aimed to evaluate whether cellular extracts obtained from plasmodium berghei-infected erythrocytes (pbx) modulate dcs phenotypically and functionally and the potential therapeutic usage of pbx-modulated dcs in the control of experimental autoimmune encephalomyelitis (eae, the mo ...	2014	24689455
in vivo antimalarial efficacy of acetogenins, alkaloids and flavonoids enriched fractions from annona crassiflora mart.	annona crassiflora and annonaceae plants are known to be used to treat malaria by traditional healers. in this work, the antimalarial efficacy of different fractions of a. crassiflora, particularly acetogenin, alkaloids and flavonoid-rich fractions, was determined in vivo using plasmodium berghei-infected mice model and toxicity was accessed by brine shrimp assay. the a. crassiflora fractions were administered at doses of 12.5 mg/kg/day in a 4-day test protocol. the results showed that some frac ...	2014	24678811
differential role of t regulatory and th17 in swiss mice infected with plasmodium berghei anka and plasmodium yoelii.	the outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. host immune responses in disease including malaria are finely regulated by the opposing effects of th17 and t regulatory (treg) cells. here we have examined the role of treg cells and th17 cells during malaria infection and find that low levels of treg cells possibly influence the outcome of infections with the lethal strain of plasmodium berghei anka (pba). in contrast, h ...	2014	24675415
parasite densities modulate susceptibility of mice to cerebral malaria during co-infection with schistosoma japonicum and plasmodium berghei.	malaria and schistosomiasis are endemic and co-exist in the same geographic areas, even co-infecting the same host. previous studies have reported that concomitant infection with schistosoma japonicum could offer protection against experimental cerebral malaria (ecm) in mice. this study was performed to evaluate whether alterations in parasite density could alter this protective effect.	2014	24670210
influence of formulation ratio of the plant components on the antimalarial properties of mama decoction.	mangifera indica, alstonia boonei, morinda lucida and azadirachta indica (mama) decoction, commonly prepared and used in nigeria from 1:1:1:1 ratio of mangifera indica l. (anacardiaceae), alstonia boonei de wild (apocynaceae), morinda lucida benth (rubiaceae), and azadirachta indica a. juss (meliaceae) leaves, plus four new variants of this combination were subjected to three in vivo antimalarial test models using chloroquine-sensitive plasmodium berghei berghei to determine the most active unde ...	2014	24658658
the plasmodium protein p113 supports efficient sporozoite to liver stage conversion in vivo.	invasive stages of plasmodium parasites possess distinct integral and peripheral membrane proteins that mediate host cell attachment and invasion. p113 is an abundant protein in detergent-resistant high molecular weight complexes in plasmodium schizonts, but is unusual since expression extends to gametocytes and sporozoites. in this study, we tested whether p113 performs important functions for parasite propagation in plasmodium berghei. we show that pre-erythrocytic expression of p113 displays ...	2014	24657782
production, fate and pathogenicity of plasma microparticles in murine cerebral malaria.	in patients with cerebral malaria (cm), higher levels of cell-specific microparticles (mp) correlate with the presence of neurological symptoms. mp are submicron plasma membrane-derived vesicles that express antigens of their cell of origin and phosphatidylserine (ps) on their surface, facilitating their role in coagulation, inflammation and cell adhesion. in this study, the in vivo production, fate and pathogenicity of cell-specific mp during plasmodium berghei infection of mice were evaluated. ...	2014	24651155
in vivo and in vitro antimalarial activity of bergenin.	malaria is a potentially life-threatening protozoal parasitic disease transmitted by female anopheles mosquitoes. drug therapy is currently the most widely used method for the control and treatment of this disease. several plants were found to contain substances possessing antimalarial properties. in this study, we investigated the antimalarial activity of bergenin, a sesquiterpene lactone compound derived from rodgersia aesculifolia batal. the results indicated that bergenin effectively inhibit ...	2014	24649107
increased survival in b-cell-deficient mice during experimental cerebral malaria suggests a role for circulating immune complexes.	the pathogenesis of malaria, an insect-borne disease that takes millions of lives every year, is still not fully understood. complement receptor 1 (cr1) has been described as a receptor for plasmodium falciparum, which causes cerebral malaria in humans. we investigated the role of cr1 in an experimental model of cerebral malaria. transgenic mice expressing human cr1 (hcr1(+)) on erythrocytes were infected with plasmodium berghei anka and developed cerebral malaria. no difference in survival was ...	2014	24643866
bioassay-guided isolation and characterization of active antiplasmodial compounds from murraya koenigii extracts against plasmodium falciparum and plasmodium berghei.	malaria is an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. currently, there is inadequate armoury of drugs for the treatment of malaria. this underscores the continuing need for the discovery and development of new effective and safe antimalarial drugs. to evaluate the in vitro and in vivo antimalarial activity of the leaf ethyl acetate extract of murraya koenigii, bioassay-guided chromatographic fractionation was emplo ...	2014	24638906
mitochondrial inactivation by anopheles albimanus cecropin 3: molecular mechanisms.	cecropin 3 (ccrp3) is an antimicrobial peptide from anopheles albimanus, which is expressed during plasmodium berghei infection. here, we report that synthetic ccrp3, aside from antibacterial activity, also shows cardio regulatory functions. in rats, ccrp3 significantly diminishes blood pressure as well as the heartbeat frequency at nanomolar concentration. ccrp3 affect the rat cardiac muscle mitochondria, inducing uncoupling of oxidative phosphorylation, oxygen consumption and transport of ca(2 ...	2014	23880546
treatment of pregnant balb/c mice with sulphadoxine pyrimethamine or chloroquine abrogates plasmodium berghei induced placental pathology.	malaria infection during pregnancy is a risk factor for foetus survival and is associated with abortion, premature delivery and low birth weight of infants in malaria endemic regions. in these regions, prophylactic measures and treatment mainly rely on chloroquine and sulphadoxine pyrimethamine, but their efficacy in reducing the placental pathology has not been studied. therefore, the present study was designed to assess the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment ...	2014	24013006
plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors.	low reticulocytosis, indicating reduced red blood cell (rbc) output, is an important feature of severe malarial anemia. evidence supports a role for plasmodium products, especially hemozoin (hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear. here, we demonstrated that low reticulocytosis and suppressed erythropoietin (epo)-induced erythropoiesis are features of malarial anemia in plasmodium yoelii- and plasmodium berghei anka-infected mice, similar t ...	2014	23922378
nanoparticle formulations of decoquinate increase antimalarial efficacy against liver stage plasmodium infections in mice.	decoquinate has potent activity against both plasmodium hepatic development and red cell replication when tested in vitro. decoquinate, however, is practically insoluble in water. to achieve its maximal in vivo efficacy, we generated nanoparticle formulations of decoquinate with a mean particle size less than 400 nm. three separate preparations at doses of decoquinate 0.5-5 mg/kg were examined in mice infected with plasmodium berghei. oral administration of nanoparticle decoquinate at a dose of ...	2014	23891618
anti-relapse activity of mirincamycin in the plasmodium cynomolgi sporozoite-infected rhesus monkey model.	mirincamycin is a close analog of the drug clindamycin used to treat plasmodium falciparum blood stages. the clinical need to treat plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.	2014	25326032
scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers.	hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (g6pd) activity is the major limitation of primaquine (pq), the only antimalarial drug in clinical use for treatment of relapsing plasmodium vivax malaria. pq is currently clinically used in its racemic form. a scalable procedure was developed to resolve racemic pq, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. these enantiomers were ...	2014	24913163
in vivo antimalarial activity of the crude leaf extract and solvent fractions of croton macrostachyus hocsht. (euphorbiaceae) against plasmodium berghei in mice.	the issue of resistance in malarial infection makes development of novel drugs a necessity. an alternative source for discovering such drugs is natural products. croton macrostachyus h. (euphorbiaceae) is used in ethiopian folklore medicine for the treatment of malaria and found to possess antimalarial activity in vitro. however, no further scientific investigations have been carried out to substantiate the claim. this study therefore aimed at investigating the in vivo antiplasmodial activity of ...	2014	24580778
maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine borrelia and plasmodium co-infection model.	in the plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. in this study, we investigated the immune responses in balb/c mice, co-infected with plasmodium berghei nk65 parasites and the relapsing fever bacterium borrelia duttonii. in contras ...	2014	25075973
in depth annotation of the anopheles gambiae mosquito midgut transcriptome.	genome sequencing of anopheles gambiae was completed more than ten years ago and has accelerated research on malaria transmission. however, annotation needs to be refined and verified experimentally, as most predicted transcripts have been identified by comparative analysis with genomes from other species. the mosquito midgut-the first organ to interact with plasmodium parasites-mounts effective antiplasmodial responses that limit parasite survival and disease transmission. high-throughput illum ...	2014	25073905
innexin agap001476 is critical for mediating anti-plasmodium responses in anopheles mosquitoes.	the toll and imd pathways are known to be induced upon plasmodium berghei and plasmodium falciparum infection, respectively. it is unclear how plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. this study examined whether innexins, gap ju ...	2014	25035430
transcriptome-wide analysis of microrna expression in the malaria mosquito anopheles gambiae.	micrornas (mirnas) are a highly abundant class of small noncoding regulatory rnas that post-transcriptionally regulate gene expression in multicellular organisms. mirnas are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. small-scale studies of mirna expression in the malaria mosquito anopheles gambiae have been reported, however no comprehensive analysis of mirnas has been performed so far.	2014	24997592
genetic ablation of plasmodj1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production.	malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multistage development in diverse environments. to gain insights into the parasite's stress response mechanisms, we investigated a conserved plasmodium protein, which we have named plasmodj1 on the basis of the presence of a putative cysteine protease motif of the dj-1/pfpi superfamily, for its activities, potential to respond to stresses and role in parasite development. plasmodj1 is expr ...	2014	25097910
genetic ablation of plasmodj1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production.	malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multistage development in diverse environments. to gain insights into the parasite's stress response mechanisms, we investigated a conserved plasmodium protein, which we have named plasmodj1 on the basis of the presence of a putative cysteine protease motif of the dj-1/pfpi superfamily, for its activities, potential to respond to stresses and role in parasite development. plasmodj1 is expr ...	2014	25091419
[study on ficolin-a against infection of plasmodium berghei in mouse model].	to evaluate the effect of ficolin-a, a lectin complement against plasmodium berghei in mice model.	2014	24822364
anopheles gambiae eicosanoids modulate plasmodium berghei survival from oocyst to salivary gland invasion.	eicosanoids affect the immunity of several pathogen/insect models, but their role on the anopheles gambiae response to plasmodium is still unknown. plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (in), or a substrate, arachidonic acid (aa), at day 7 or day 12 post-infection (p.i.). salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. in promoted infection upon sporozoite release from oocysts, but inhibited infectio ...	2014	25141285
anopheles gambiae blood feeding initiates an anticipatory defense response to plasmodium berghei.	mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. much remains unknown about how different pathogens are sensed and specific responses triggered. leucine-rich repeat immune proteins (lrims) are a mosquito-specific family of putative innate receptors. although some lrims have been implicated in mosquito immune responses, the function of most family members is largely unknown. we screened anopheles gambiae lrims by rnai for effects on mosquito ...	2014	25247883
characterization of plasmodium developmental transcriptomes in anopheles gambiae midgut reveals novel regulators of malaria transmission.	the passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. here, we used dna microarrays to profile the developmental transcriptomes of the rodent malaria parasite plasmodium berghei in vivo, in the midgut of anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. data analysis identified several distinct transcriptional programmes en ...	2014	25225164
an essential role of the basal body protein sas-6 in plasmodium male gamete development and malaria transmission.	gametocytes are the sole plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. flagellum assembly of the plasmodium male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. the centriole/basal body protein sas-6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ ...	2014	25154861
a serine protease homolog negatively regulates tep1 consumption in systemic infections of the malaria vector anopheles gambiae.	clip domain serine protease homologs are widely distributed in insect genomes and play important roles in regulating insect immune responses, yet their exact functions remain poorly understood. here, we show that clipa2, a clip domain serine protease homolog of anopheles gambiae, regulates the consumption of the mosquito complement-like protein tep1 during systemic bacterial infections. we provide evidence that clipa2 localizes to microbial surfaces in a tep1-dependent manner whereby it negative ...	2014	25012124
in vitro activity of waladin benzimidazoles against different life cycle stages of plasmodium parasites.	waladin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from wolbachia endobacteria of filarial nematodes. we report that waladin1 and two derivatives killed blood stage plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μm, respectively). one of these derivatives inhibited gliding motility of plasmodium berghei anka infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic r ...	2014	25313210
lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations.	to achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. to this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). consequently, any reduction in new infections due to drug treatment ...	2014	25385107
plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.	the invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. the pellicle is characterised by a double-layered 'inner membrane complex' (imc) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (spn). the spn consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. here, we re-appraise ...	2014	25475193
experimental cerebral malaria pathogenesis--hemodynamics at the blood brain barrier.	cerebral malaria claims the lives of over 600,000 african children every year. to better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, plasmodium berghei anka (pba) infected cba/caj mice, which develop experimental cerebral malaria (ecm), and p. yoelii 17xl (pyxl) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. using a combination of intravital im ...	2014	25474413
the repeat region of the circumsporozoite protein is critical for sporozoite formation and maturation in plasmodium.	the circumsporozoite protein (csp) is the major surface protein of the sporozoite stage of malaria parasites and has multiple functions as the parasite develops and then migrates from the mosquito midgut to the mammalian liver. the overall structure of csp is conserved among plasmodium species, consisting of a species-specific central tandem repeat region flanked by two conserved domains: the nh2-terminus and the thrombospondin repeat (tsr) at the cooh-terminus. although the central repeat regio ...	2014	25438048
visualization of malaria parasites in the skin using the luciferase transgenic parasite, plasmodium berghei.	we produced a transgenic rodent malaria parasite (plasmodium berghei) that contained the luciferase gene under a promoter region of elongation factor-1α. these transgenic (tg) parasites expressed luciferase in all stages of their life cycle, as previously reported. however, we were the first to succeed in observing sporozoites as a mass in mouse skin following their deposition by the probing of infective mosquitoes. our transgenic parasites may have emitted stronger bioluminescence than previous ...	2014	25859153
genome-wide rip-chip analysis of translational repressor-bound mrnas in the plasmodium gametocyte.	following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. during sexual development of plasmodium berghei, a rodent model for human malaria species including p. falciparum, the stability of repressed mrnas requires the translational repressors dozi and cith. when these repressors are absent, plasmodium zygote development and transmission to the ...	2014	25418785
zipco, a putative metal ion transporter, is crucial for plasmodium liver-stage development.	the malaria parasite, plasmodium, requires iron for growth, but how it imports iron remains unknown. we characterize here a protein that belongs to the zip (zrt-, irt-like protein) family of metal ion transport proteins and have named zip domain-containing protein (zipco). inactivation of the zipco-encoding gene in plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. iron/zi ...	2014	25257508
a cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.	plasmodium parasites express a potent inhibitor of cysteine proteases (icp) throughout their life cycle. to analyze the role of icp in different life cycle stages, we generated a stage-specific knockout of the plasmodium berghei icp (pbicp). excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual pbicp protein being detectable in sporozoites. the vast majority of these parasites invading a cultured hepatocyte cell ...	2014	25166051
host pi(3,5)p2 activity is required for plasmodium berghei growth during liver stage infection.	malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. in the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (pvm). here, we dissected the interaction between the plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (pikfyve) that converts phosphatidylinositol 3-phosphate [pi(3)p] into phosphatidylinositol 3,5-bisphospha ...	2014	24992508
vectored antibody gene delivery protects against plasmodium falciparum sporozoite challenge in mice.	malaria caused by plasmodium falciparum kills nearly one million children each year and imposes crippling economic burdens on families and nations worldwide. no licensed vaccine exists, but infection can be prevented by antibodies against the circumsporozoite protein (csp), the major surface protein of sporozoites, the form of the parasite injected by mosquitoes. we have used vectored immunoprophylaxis (vip), an adeno-associated virus-based technology, to introduce preformed antibody genes encod ...	2014	25114213
antigen export during liver infection of the malaria parasite augments protective immunity.	protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. intracellular plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class i (mhc-i) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. whether exported liver-stage proteins constitute better candidates for mhc-i antigen presentation to cd8(+) t lymphocytes remains unknown. here, we systematica ...	2014	25073641
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
assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections.	as anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malaria infections. the us army is developing tafenoquine (tq), an analogue of primaquine (pq), which is expected to be more effective in preventing malaria in deployed military personnel.	2014	24731238
cd8+ t cells eliminate liver-stage plasmodium berghei parasites without detectable bystander effect.	immunization with attenuated plasmodium sporozoites or viral vectored vaccines can induce protective cd8(+) t cells that can find and eliminate liver-stage malaria parasites. a key question is whether cd8(+) t cells must recognize and eliminate each parasite in the liver or whether bystander killing can occur. to test this, we transferred antigen-specific effector cd8(+) t cells to mice that were then coinfected with two plasmodium berghei strains, only one of which could be recognized directly ...	2014	24421043
phenotypic characterization of plasmodium berghei responsive cd8+ t cells after immunization with live sporozoites under chloroquine cover.	an effective malaria vaccine remains elusive. the most effective experimental vaccines confer only limited and short-lived protection despite production of protective antibodies. however, immunization with irradiated sporozoites, or with live sporozoites under chloroquine cover, has resulted in long-term protection apparently due to the generation of protective cd8+ t cells. the nature and function of these protective cd8+ t cells has not been elucidated. in the current study, the phenotype of c ...	2014	24620841
phosphoinositide metabolism links cgmp-dependent protein kinase g to essential ca²⁺ signals at key decision points in the life cycle of malaria parasites.	many critical events in the plasmodium life cycle rely on the controlled release of ca²⁺ from intracellular stores to activate stage-specific ca²⁺-dependent protein kinases. using the motility of plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cgmp)-dependent protein kinase, pkg, maintains the elevated level of cytosolic ca²⁺ required for gliding motility. we find that the same pkg-dependent pathway operates upstream of the ca²⁺ signals tha ...	2014	24594931
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
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
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
a cascade of dna-binding proteins for sexual commitment and development in plasmodium.	commitment to and completion of sexual development are essential for malaria parasites (protists of the genus plasmodium) to be transmitted through mosquitoes. the molecular mechanism(s) responsible for commitment have been hitherto unknown. here we show that pbap2-g, a conserved member of the apicomplexan ap2 (apiap2) family of dna-binding proteins, is essential for the commitment of asexually replicating forms to sexual development in plasmodium berghei, a malaria parasite of rodents. pbap2-g ...	2014	24572359
whole pichia pastoris yeast expressing measles virus nucleoprotein as a production and delivery system to multimerize plasmodium antigens.	yeasts are largely used as bioreactors for vaccine production. usually, antigens are produced in yeast then purified and mixed with adjuvants before immunization. however, the purification costs and the safety concerns recently raised by the use of new adjuvants argue for alternative strategies. to this end, the use of whole yeast as both production and delivery system appears attractive. here, we evaluated pichia pastoris yeast as an alternative vaccine production and delivery system for the ci ...	2014	24475165
simple, sensitive and quantitative bioluminescence assay for determination of malaria pre-patent period.	the first phase of malaria infection occurs in the liver and is clinically silent. inside hepatocytes each plasmodium sporozoite replicate into thousands of erythrocyte-infectious merozoites that when released into the blood stream result in clinical symptoms of the disease. the time between sporozoite inoculation and the appearance of parasites in the blood is defined as the pre-patent period, which is classically analysed by time-consuming and labor-intensive techniques, such as microscopy and ...	2014	24400642
tafenoquine and npc-1161b require cyp 2d metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.	tafenoquine (tq) is an 8-aminoquinoline (8aq) that has been tested in several phase ii and phase iii clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. npc-1161b is a promising 8aq in late preclinical development. it has recently been reported that the 8aq drug primaquine requires metabolic activation by cyp 2d6 for efficacy in humans and in mice, highlighting the importance of pharmacogenomics in the target population when administering primaquin ...	2014	24386891
stress granules and plasmodium liver stage infection.	organisms have evolved numerous strategies to control infection by an array of intracellular pathogens. one cell autonomous pathogen control strategy is global inhibition of protein synthesis via stress granule (sg) formation. sgs are induced by stressful stimuli such as oxidative stress and nutrient deprivation, and are known to counteract both viral and bacterial infections. pathogens, in turn, may actively block an infected cell's ability to form sgs. in vitro and in vivo, many liver stage ma ...	2014	24357231
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
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
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
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
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
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
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
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
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
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
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
copper-transporting atpase is important for malaria parasite fertility.	homeostasis of the trace element copper is essential to all eukaryotic life. copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. here, we describe the functional characterization of an evolutionarily highly conserved, predicted copper-transporting p-type atpase (cutp) in the murine malaria model parasite plasmodium berghei. live imaging of a parasite line expressing a fluorescently tagged ...	2013	24237419
the malarial serine protease sub1 plays an essential role in parasite liver stage development.	transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. the resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. these are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. whilst elements of liver stage merozoite biology are similar to those in the much bette ...	2013	24348254
hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.	homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. in vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possib ...	2013	24291761
inhibitor of cysteine proteases is critical for motility and infectivity of plasmodium sporozoites.	malaria is transmitted when motile sporozoites are injected into the dermis by an infected female anopheles mosquito. inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. parasite-encoded factors with exclusive vital roles in the insect vector can be studied by classical reverse genetics. here, we characterized the in vivo roles of plasmodium berghei falstatin/icp (inhibitor of cysteine proteases). this protei ...	2013	24281719
a small molecule glycosaminoglycan mimetic blocks plasmodium invasion of the mosquito midgut.	malaria transmission-blocking (t-b) interventions are essential for malaria elimination. small molecules that inhibit the plasmodium ookinete-to-oocyst transition in the midgut of anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. chondroitin sulfate glycosaminoglycans (cs-gags) on the anopheles gambiae midgut surface are putative ligands for plasmodium falciparum ookinetes. we hypothesized that our synthetic polysulfonated polymer, vs1, acting as a ...	2013	24278017
plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.	plasmodium calcium dependent protein kinase (cdpk1) is required for the development of sexual stages in the mosquito. in addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. we demonstrate that plasmodium berghei cdpk1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. we successfully disrupted p. berghei cdpk1 (pbcdpk1) by homologous recombination. the reco ...	2013	24265753
trem2 governs kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.	plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (trem2) and mhc class ii molecules as determinants of plasmodium berghei liver stage infection in mice. locus belr1 confers resistance to malaria liver stage infection. the use of newly derived subcongenic mouse lines allo ...	2013	24218563
cd8+ t cells specific for a malaria cytoplasmic antigen form clusters around infected hepatocytes and are protective at the liver stage of infection.	following anopheles mosquito-mediated introduction into a human host, plasmodium parasites infect hepatocytes and undergo intensive replication. accumulating evidence indicates that cd8(+) t cells induced by immunization with attenuated plasmodium sporozoites can confer sterile immunity at the liver stage of infection; however, the mechanisms underlying this protection are not clearly understood. to address this, we generated recombinant plasmodium berghei anka expressing a fusion protein of an ...	2013	23897612
comparative susceptibility of different biological forms of anopheles stephensi to plasmodium berghei anka strain.	there are varying degrees of compatibility between malaria parasite-mosquito species, and understanding this compatibility may be crucial for developing effective transmission-blocking vaccines. this study investigates the compatibility of different biological forms of a malaria vector, anopheles stephensi, to plasmodium berghei anka strain.	2013	24086525
expression profiling of plasmodium berghei hsp70 genes for generation of bright red fluorescent parasites.	live cell imaging of recombinant malarial parasites encoding fluorescent probes provides critical insights into parasite-host interactions and life cycle progression. in this study, we generated a red fluorescent line of the murine malarial parasite plasmodium berghei. to allow constitutive and abundant expression of the mcherry protein we profiled expression of all members of the p. berghei heat shock protein 70 (hsp70) family. we identified pbhsp70/1, an invariant ortholog of plasmodium falcip ...	2013	24013507
development of a chimeric plasmodium berghei strain expressing the repeat region of the p. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.	the development of vaccine candidates against plasmodium vivax-the most geographically widespread human malaria species-is challenged by technical difficulties, such as the lack of in vitro culture systems and availability of animal models. chimeric rodent plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. we report the successful development and characterization of chimeric plasmodium berghei parasites bearing the type i repeat region of p ...	2013	23716612
immunisation against a serine protease inhibitor reduces intensity of plasmodium berghei infection in mosquitoes.	the mosquito innate immune response is able to clear the majority of plasmodium parasites. this immune clearance is controlled by a number of regulatory molecules including serine protease inhibitors (serpins). to determine whether such molecules could represent a novel target for a malaria transmission-blocking vaccine, we vaccinated mice with anopheles gambiae serpin-2. antibodies against anopheles gambiae serpin-2 significantly reduced the infection of a heterologous anopheles species (anophe ...	2013	23872520
morphogenesis of plasmodium zoites is uncoupled from tensile strength.	a shared feature of the motile stages (zoites) of malaria parasites is a cortical cytoskeletal structure termed subpellicular network (spn), thought to define and maintain cell shape. plasmodium alveolins comprise structural components of the spn, and alveolin gene knockout causes morphological abnormalities that coincide with markedly reduced tensile strength of the affected zoites, indicating the alveolins are prime cell shape determinants. here, we characterize a novel spn protein of plasmodi ...	2013	23773015
the etramp family member sep2 is expressed throughout plasmodium berghei life cycle and is released during sporozoite gliding motility.	the early transcribed membrane proteins etramps belong to a family of small, transmembrane molecules unique to plasmodium parasite, which share a signal peptide followed by a short lysine-rich stretch, a transmembrane domain and a variable, highly charged c-terminal region. etramps are usually expressed in a stage-specific manner. in the blood stages they localize to the parasitophorous vacuole membrane and, in described cases, to vesicle-like structures exported to the host erythrocyte cytosol. ...	2013	23840634
the metabolism of primaquine to its active metabolite is dependent on cyp 2d6.	the efficacy of the 8-aminoquinoline (8aq) drug primaquine (pq) has been historically linked to cyp-mediated metabolism. although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for cyp 2d6 in the generation of redox active metabolites.	2013	23782898
transgenic parasites stably expressing full-length plasmodium falciparum circumsporozoite protein as a model for vaccine down-selection in mice using sterile protection as an endpoint.	circumsporozoite protein (csp) of plasmodium falciparum is a protective human malaria vaccine candidate. there is an urgent need for models that can rapidly down-select novel csp-based vaccine candidates. in the present study, the mouse-mosquito transmission cycle of a transgenic plasmodium berghei malaria parasite stably expressing a functional full-length p. falciparum csp was optimized to consistently produce infective sporozoites for protection studies. a minimal sporozoite challenge dose wa ...	2013	23536694
identification of targets of cd8⁺ t cell responses to malaria liver stages by genome-wide epitope profiling.	cd8⁺ t cells mediate immunity against plasmodium liver stages. however, the paucity of parasite-specific epitopes of cd8⁺ t cells has limited our current understanding of the mechanisms influencing the generation, maintenance and efficiency of these responses. to identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic profiling of h(2b)-restricted peptides predicted from genome-wide analysis. we describe the identification of plasmodium berghei (pb ...	2013	23675294
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
efficacy of a plasmodium vivax malaria vaccine using chad63 and modified vaccinia ankara expressing thrombospondin-related anonymous protein as assessed with transgenic plasmodium berghei parasites.	plasmodium vivax is the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in southeast asia and latin america. despite this dramatic burden, very few vaccines have been assessed in humans. the clinically relevant vectors modified vaccinia virus ankara (mva) and the chimpanzee adenovirus chad63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to in ...	2013	24379295
dihydroquinazolinone inhibitors of proliferation of blood and liver stage malaria parasites.	drugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds--dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles--with promising activity against the liver stage. focused structure-activity studies on the dihydroquinazolinone scaffol ...	2013	24366746