Publications

TitleAbstractYear
Filter
PMID
Filter
development of an in vitro assay and demonstration of plasmodium berghei liver-stage inhibition by trap-specific cd8+ t cells.the development of an efficacious vaccine against the plasmodium parasite remains a top priority. previous research has demonstrated the ability of a prime-boost virally vectored sub-unit vaccination regimen, delivering the liver-stage expressed malaria antigen trap, to produce high levels of antigen-specific t cells. the liver-stage of malaria is the main target of t cell-mediated immunity, yet a major challenge in assessing new t cell inducing vaccines has been the lack of a suitable pre-clini ...201525822951
resisting infection by plasmodium berghei increases the sensitivity of the malaria vector anopheles gambiae to ddt.the evolution of insecticide resistance threatens current malaria control methods, which rely heavily on chemical insecticides. the magnitude of the threat will be determined by the phenotypic expression of resistance in those mosquitoes that can transmit malaria. these differ from the majority of the mosquito population in two main ways; they carry sporozoites (the infectious stage of the plasmodium parasite) and they are relatively old, as they need to survive the development period of the mal ...201525888982
studying the effect of chloroquine on sporozoite-induced protection and immune responses in plasmodium berghei malaria.sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (cps-cq) efficiently induces sterile protection against malaria. in humans, cps-cq is strikingly more efficient than immunization with radiation attenuated sporozoites (ras), raising the hypothesis that this might be partially due to cq. chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. the aim of this stu ...201525889324
mitochondrial atp synthase is dispensable in blood-stage plasmodium berghei rodent malaria but essential in the mosquito phase.mitochondrial atp synthase is driven by chemiosmotic oxidation of pyruvate derived from glycolysis. blood-stage malaria parasites eschew chemiosmosis, instead relying almost solely on glycolysis for their atp generation, which begs the question of whether mitochondrial atp synthase is necessary during the blood stage of the parasite life cycle. we knocked out the mitochondrial atp synthase β subunit gene in the rodent malaria parasite, plasmodium berghei, ablating the protein that converts adp t ...201525831536
the plasmodium class xiv myosin, myob, has a distinct subcellular location in invasive and motile stages of the malaria parasite and an unusual light chain.myosin b (myob) is one of the two short class xiv myosins encoded in the plasmodium genome. class xiv myosins are characterized by a catalytic "head," a modified "neck," and the absence of a "tail" region. myosin a (myoa), the other class xiv myosin in plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but myob is not well characterized. we analyzed the properties of myob using three parasite species as follows: plasmodium falciparu ...201525802338
a plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane.the coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread of an infection. while phospholipases have been shown to play important roles in bacteria host cell egress and virulence, their role in the release of intracellular eukaryotic parasites is largely unknown. we examined a malaria parasite protein with phospholipase activity and found it to be involved in hepatocyte egress. in hepatocytes, plasmodium parasites are surrounded by a parasito ...201525786000
pivotal and distinct role for plasmodium actin capping protein alpha during blood infection of the malaria parasite.accurate regulation of microfilament dynamics is central to cell growth, motility and response to environmental stimuli. stabilizing and depolymerizing proteins control the steady-state levels of filamentous (f-) actin. capping protein (cp) binds to free barbed ends, thereby arresting microfilament growth and restraining elongation to remaining free barbed ends. in all cps characterized to date, alpha and beta subunits form the active heterodimer. here, we show in a eukaryotic parasitic cell tha ...201525565321
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 ...201425313210
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 ...201425385107
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 ...201425475193
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 ...201425474413
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 ...201425438048
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 ...201425859153
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 ...201425418785
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 ...201425257508
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 ...201425166051
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 ...201424992508
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 ...201425114213
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 ...201425073641
genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation.reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (pps) during plasmodium development are unknown. we report a functional analysis of the plasmodium berghei protein phosphatome, which exhibits high conservation with the p. falciparum phosphatome and comprises 30 predicted pps with differential and distinct expression patt ...025011111
engineered single nucleotide polymorphisms in the mosquito mek docking site alter plasmodium berghei development in anopheles gambiae.susceptibility to plasmodium infection in anopheles gambiae has been proposed to result from naturally occurring polymorphisms that alter the strength of endogenous innate defenses. despite the fact that some of these mutations are known to introduce non-synonymous substitutions in coding sequences, these mutations have largely been used to rationalize knockdown of associated target proteins to query the effects on parasite development in the mosquito host. here, we assay the effects of engineer ...201424957684
species-specific escape of plasmodium sporozoites from oocysts of avian, rodent, and human malarial parasites.malaria is transmitted when an infected mosquito delivers plasmodium sporozoites into a vertebrate host. there are many species of plasmodium and, in general, the infection is host-specific. for example, plasmodium gallinaceum is an avian parasite, while plasmodium berghei infects mice. these two parasites have been extensively used as experimental models of malaria transmission. plasmodium falciparum and plasmodium vivax are the most important agents of human malaria, a life-threatening disease ...201627480269
an antibody against an anopheles albimanus midgut myosin reduces plasmodium berghei oocyst development.malaria parasites are transmitted by anopheles mosquitoes. although several studies have identified mosquito midgut surface proteins that are putatively important for plasmodium ookinete invasion, only a few have characterized these protein targets and demonstrated transmission-blocking activity. molecular information about these proteins is essential for the development of transmission-blocking vaccines (tbv). the aim of the present study was to test three monoclonal antibodies (mabs), a-140, a ...201627165123
marked biological differences between insecticide resistant and susceptible strains of anopheles funestus infected with the murine parasite plasmodium berghei.anopheles funestus is one of the major malaria vectors in africa but research on this species has been restricted due to the lack of viable laboratory colonies. the vectorial capacity of natural populations of an. funestus is well known but its ability to host plasmodium in the laboratory and the development cycle of the parasite within this mosquito species was, until very recently, unknown. in this study we compared laboratory strains of an. funestus that were resistant and susceptible to pyre ...201323782642
wild anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, plasmodium berghei.malaria parasites undergo complex developmental transitions within the mosquito vector. a commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, p. berghei. anopheles funestus is a major malaria vector in sub-saharan africa but has received less attention than the sympatric species, anopheles gambiae. the imminent completion of the a. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in th ...201323593423
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 ...201425141285
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 ...201425247883
infection with plasmodium berghei ookinetes alters protein expression in the brain of anopheles albimanus mosquitoes.the behaviour of anopheles spp. mosquitoes, vectors for plasmodium parasites, plays a crucial role in the propagation of malaria to humans. consequently, it is important to understand how the behaviour of these mosquitoes is influenced by the interaction between the brain and immunological status. the nervous system is intimately linked to the immune and endocrine systems. there is evidence that the malaria parasite alters the function of these systems upon infecting the mosquito. although there ...201627724938
novel factors of anopheles gambiae haemocyte immune response to plasmodium berghei infection.insect haemocytes mediate cellular immune responses (e.g., phagocytosis) and contribute to the synthesis of humoral immune factors. in previous work, a genome-wide molecular characterization of anopheles gambiae circulating haemocytes was followed by functional gene characterization using cell-based rnai screens. assays were carried out to investigate the role of selected haemocyte-specific or enriched genes in phagocytosis of bacterial bio-particles, expression of the antimicrobial peptide cecr ...201626858200
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 ...201425012124
in vitro and in vivo antimalarial activity and cytotoxicity of extracts, fractions and a substance isolated from the amazonian plant tachia grandiflora (gentianaceae).tachia sp. are used as antimalarials in the amazon region and in vivo antimalarial activity of a tachia sp. has been previously reported. tachia grandiflora maguire and weaver is an amazonian antimalarial plant and herein its cytotoxicity and antimalarial activity were investigated. spectral analysis of the tetraoxygenated xanthone decussatin and the iridoid aglyone amplexine isolated, respectively, from the chloroform fractions of root methanol and leaf ethanol extracts was performed. in vitro ...023827996
bacteria- and imd pathway-independent immune defenses against plasmodium falciparum in anopheles gambiae.the mosquito anopheles gambiae uses its innate immune system to control bacterial and plasmodium infection of its midgut tissue. the activation of potent imd pathway-mediated anti-plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, pgrplc. we employed transcriptomic and reverse genetic analyses to compare the p. falciparum infection-responsive transcriptomes o ...201324019865
targeted mutagenesis in the malaria mosquito using tale nucleases.anopheles gambiae, the main mosquito vector of human malaria, is a challenging organism to manipulate genetically. as a consequence, reverse genetics studies in this disease vector have been largely limited to rna interference experiments. here, we report the targeted disruption of the immunity gene tep1 using transgenic expression of transcription-activator like effector nucleases (talens), and the isolation of several tep1 mutant a. gambiae lines. these mutations inhibited protein production a ...201323977401
hemozoin activates the innate immune system and reduces plasmodium berghei infection in anopheles gambiae.malaria is a worldwide infectious disease caused by plasmodium parasites and transmitted by female anopheles mosquitoes. the malaria vector mosquito anopheles can trigger effective mechanisms to control completion of the plasmodium lifecycle; the mosquito immune response to the parasite involves several pathways which are not yet well characterized. plasmodium metabolite hemozoin has emerged as a potent immunostimulator of mammalian tissues. in this study, we aim to investigate the role of this ...201525573379
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 ...201425225164
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/ ...201425154861
targeting molecular interactions essential for plasmodium sexual reproduction.malaria remains one of the most devastating infectious diseases, killing up to a million people every year. whereas much progress has been made in understanding the life cycle of the parasite in the human host and in the mosquito vector, significant gaps of knowledge remain. fertilization of malaria parasites, a process that takes place in the lumen of the mosquito midgut, is poorly understood and the molecular interactions (receptor-ligand) required for plasmodium fertilization remain elusive. ...201525944054
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 ...201425073905
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 ...201425035430
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.201424997592
the role of hemocytes in anopheles gambiae antiplasmodial immunity.hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. the effect of activating toll signaling in hemocytes on plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. these transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the ...201323886925
transcriptional silencing and activation of paternal dna during plasmodium berghei zygotic development and transformation to oocyst.the malaria parasite develops sexually in the mosquito midgut upon entry with the ingested blood meal before it can invade the midgut epithelium and embark on sporogony. recent data have identified a number of distinct transcriptional programmes operating during this critical phase of the parasite life cycle. we aimed at characterizing the parental contribution to these transcriptional programmes and establish the genetic framework that would guide further studies of plasmodium zygotic developme ...201525728487
ectopic expression of a neospora caninum kazal type inhibitor triggers developmental defects in toxoplasma and plasmodium.regulated proteolysis is known to control a variety of vital processes in apicomplexan parasites including invasion and egress of host cells. serine proteases have been proposed as targets for drug development based upon inhibitor studies that show parasite attenuation and transmission blockage. genetic studies suggest that serine proteases, such as subtilisin and rhomboid proteases, are essential but functional studies have proved challenging as active proteases are difficult to express. protei ...201525803874
anopheles midgut frep1 mediates plasmodium invasion.malaria transmission depends on sexual stage plasmodium parasites successfully invading anopheline mosquito midguts following a blood meal. however, the molecular mechanisms of plasmodium invasion of mosquito midguts have not been fully elucidated. previously, we showed that genetic polymorphisms in the fibrinogen-related protein 1 (frep1) gene are significantly associated with plasmodium falciparum infection in anopheles gambiae, and frep1 is important for plasmodium berghei infection of mosqui ...201525991725
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.201425326032
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 ...201424913163
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 ...201424580778
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 ...201425075973
anti-malarial and anti-inflammatory effects of gleichenia truncata mediated through inhibition of gsk3β.gleichenia truncata is a highland fern from the gleicheniaceae family known for its traditional use among indigenous communities in asia to treat fever. the scientific basis of its effect has yet to be documented. a yeast-based kinase assay conducted in our laboratory revealed that crude methanolic extract (cme) of g. truncata exhibited glycogen synthase kinase-3 (gsk3)-inhibitory activity. gsk3β is now recognized to have a pivotal role in the regulation of inflammatory response during bacterial ...201526695202
production of plasmodium vivax enolase in escherichia coli and its protective properties.plasmodium vivax predominates in south-east asia and the american continent, causes significant morbidity and inflicts a huge socioeconomic burden. sequencing completion of the plasmodium vivax genome and transcriptome provides the chance to identify antigens. enolase is the eighth enzyme in the glycolytic pathway, which, apart from its glycolytic function, also possess antigenic properties and is present on the cell wall of many invasive organisms, such as candida albicans. in order to assess w ...201627487171
defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model.the interferon-inducible transmembrane (ifitm) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. further, single nucleotide polymorphisms (snps) in its sequence have been linked with risk of developing severe influenza virus infections in humans. the number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which ente ...201324278312
plasma micrornas are promising novel biomarkers for the early detection of toxoplasma gondii infection.micrornas (mirnas) have been shown to be present in plasma, which are remarkably stable, and have been suggested as disease biomarkers. toxoplasma gondii (t. gondii) is a protozoan parasite that is infective to a wide range of animals and human beings. previous studies have found that the parasite generated a large number of mirnas during proliferation and it is known that the spectrum of mirna expression in the infected hosts is pathogen-specific. to date, there are no reports regarding the app ...201425199527
magnetic nanoparticles are highly toxic to chloroquine-resistant plasmodium falciparum, dengue virus (den-2), and their mosquito vectors.a main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. we investigated the toxicity of magnetic nanoparticles (mnp) produced by magnetospirillum gryphiswaldense (strain msr-1) on chloroquine-resistant (cq-r) and sensitive (cq-s) plasmodium falciparum, dengue virus (den-2), and two of their main vectors, anopheles stephensi and aedes aegypti, respectively. mnp were studied by fourier-transform infrared spectroscopy and transmission elect ...201727815736
a 43 kda recombinant plasmepsin elicits immune response in mice against plasmodium berghei malaria.intraerythrocytic parasites degrade haemoglobin to make available nutrients for their growth and maturation. plasmepsins, the aspartic proteases of plasmodium play a significant role in haemoglobin degradation and are proposed as attractive drug targets. in the present study the gene which encodes plasmepsin in rodent malaria parasite, plasmodium berghei, was cloned and expressed. the gene was sequenced and expressed in escherichia coli bl21de3 and a recombinant plasmepsin of molecular weight 43 ...201626751879
enzymatic characterization of recombinant food vacuole plasmepsin 4 from the rodent malaria parasite plasmodium berghei.the rodent malaria parasite plasmodium berghei is a practical model organism for experimental studies of human malaria. plasmepsins are a class of aspartic proteinase isoforms that exert multiple pathological effects in malaria parasites. plasmepsins residing in the food vacuole (fv) of the parasite hydrolyze hemoglobin in red blood cells. in this study, we cloned pbpm4, the fv plasmepsin gene of p. berghei that encoded an n-terminally truncated pro-segment and the mature enzyme from genomic dna ...201526510189
phagosomal acidification prevents macrophage inflammatory cytokine production to malaria, and dendritic cells are the major source at the early stages of infection: implication for malaria protective immunity development.inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. to gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (dcs) to purified plasmodium falciparum and plasmodium berghei anka, and by spleen macrophag ...201526240140
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 ...201425097910
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 ...201425091419
[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.201424822364
potential of lichen secondary metabolites against plasmodium liver stage parasites with fas-ii as the potential target.chemicals targeting the liver stage (ls) of the malaria parasite are useful for causal prophylaxis of malaria. in this study, four lichen metabolites, evernic acid (1), vulpic acid (2), psoromic acid (3), and (+)-usnic acid (4), were evaluated against ls parasites of plasmodium berghei. inhibition of p. falciparum blood stage (bs) parasites was also assessed to determine stage specificity. compound 4 displayed the highest ls activity and stage specificity (ls ic50 value 2.3 μm, bs ic50 value 47. ...201323806111
recombination-mediated genetic engineering of plasmodium berghei dna.dna of plasmodium berghei is difficult to manipulate in escherichia coli by conventional restriction and ligation methods due to its high content of adenine and thymine (at) nucleotides. this limits our ability to clone large genes and to generate complex vectors for modifying the parasite genome. we here describe a protocol for using lambda red recombinase to modify inserts of a p. berghei genomic dna library constructed in a linear, low-copy, phage-derived vector. the method uses primer extens ...201322990774
bacteria and protozoa differentially modulate the expression of rab proteins.phagocytic cells represent an important line of innate defense against microorganisms. uptake of microorganisms by these cells involves the formation of a phagosome that matures by fusing with endocytic compartments, resulting in killing of the enclosed microbe. small gtpases of the rab family are key regulators of vesicular trafficking in the endocytic pathway. intracellular pathogens can interfere with the function of these proteins in order to subvert host immune responses. however, it is unk ...201222911692
[cloning and expression of pbtip analogous gene from plasmodium berghei anka and preparation of its polyclonal antibody].to clone and express a novel protein analogous to tip (t cell immunomodulatory protein) of plasmodium berghei anka and prepare its polyclonal antibody.200824812812
the role of pro-resolution lipid mediators in infectious disease.inflammation is an essential host defence against infection, but can be damaging when excessive. resolution of inflammation is an active process, and the pro-resolution effects of lipoxins, resolvins and protectins have received significant interest. here, we review emerging data on the role of these lipid mediators in infectious disease. lipoxins influence host control of mycobacterium tuberculosis, toxoplasma gondii, trypanosoma cruzi and plasmodium berghei cerebral malaria in mice. their effe ...201424400794
experimental systems for studying plasmodium/hiv coinfection.coinfections with human immunodeficiency virus (hiv) and plasmodium, the causative agents of aids and malaria, respectively, are frequent and their comorbidity especially in sub-saharan africa is high. while clinical studies suggest an influence of the two pathogens on the outcome of the respective infections, experimental studies on the molecular and immunological impact of coinfections are rare. this reflects the limited availability of suitable model systems that reproduce key properties of b ...201627009943
the effect of lopinavir/ritonavir on the antimalarial activity of artemether or artemether/lumefantrine in a mouse model of plasmodium berghei.the possibility of drug-drug interactions occurring during the treatment of malaria infection in human immunodeficient virus (hiv) patients receiving antiretroviral drugs is very high and limited data are available. this study reports the effect of lopinavir/ritonavir (lr) an antiretroviral drug on the antimalarial activity of standard dose of artemether/lumefantrine (al) or artemether (am) in a mouse model of plasmodium berghei. the 50% effective dose (ed50) of am alone (0.80 ± 0.15 and 2.18 ± ...201524621166
bacterium-like particles as multi-epitope delivery platform for plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice.virus-like particles have been regularly used as an antigen delivery system for a number of plasmodium peptides or proteins. the present study reports the immunogenicity and protective efficacy of bacterium-like particles (blps) generated from lactococcus lactis and loaded with plasmodium berghei circumsporozoite protein (pbcsp) peptides.201222348325
new heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents.a new series of pyrazole derivatives were synthesized by hybridization with five-membered heterocyclic moieties such as thiazoles, thiazolidinones, 1,3,4-thiadiazoles and pyrazolines. the compounds were evaluated for their in vivo antimalarial activity against plasmodium berghei infected mice and the most active derivatives were further examined for their in vitro antimalarial activity against chloroquine resistant (rkl9) strain of plasmodium falciparum. compounds 2c, 2d, 4b, 4c, 4d, 5a, 6c, 8c ...201525768697
evaluation of some 1h-pyrazole derivatives as a dual acting antimalarial and anti-leishmanial agents.the synthesis of a novel series of 1h-pyrazole derivatives was achieved by condensation of pyrazole aldehyde 1 with hydrazine hydrate to give hydrazone 7. on the other hand, cyclization of α,β-unsaturated ketone counterpart 2 using hydrazine hydrate in liquid aliphatic acids rendered compounds 4-6 and hydrazine hydrate in ethanol afforded compound 3. the later was allowed to react with aroyl chloride giving rise to compounds 8, 9. all compounds were tested for their in vivo anti-malarial and in ...201425362601
in vitro and in vivo antimalarial potential of oleoresin obtained from copaifera reticulata ducke (fabaceae) in the brazilian amazon rainforest.in view of the wide variety of the flora of the amazon region, many plants have been studied in the search for new antimalarial agents. copaifera reticulata is a tree distributed throughout the amazon region which contains an oleoresin rich in sesquiterpenes and diterpenes with β-caryophyllene as the major compound. the oleoresin has demonstrated antiparasitic activity against leishmania amazonensis. because of this previously reported activity, this oleoresin would be expected to also have anti ...201728160850
antiprotozoal screening of the cuban native plant scutellaria havanensis.scutellaria havanensis jacq. (lamiaceae) is a native medicinal herb with a history of use in cuba.201627564587
synthesis, cytotoxic activity on leukemia cell lines and quantitative structure-activity relationships (qsar) studies of morita-baylis-hillman adducts.the morita-baylis-hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential and promising biological profiles. the morita-baylis-hillman adducts (mbha) are a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs, e.g. as anti-leishmania chagasi and leishmania amazonensis, anti- trypanosoma cruzi, anti-plasmodium falciparum and pla ...201627150963
morita-baylis-hillman adducts: biological activities and potentialities to the discovery of new cheaper drugs.this review aims to present by the first time the morita-baylis-hillman adducts (mbha) as a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs. now, most these compounds can be prepared fast and on a single synthetic step (one-pot reaction) in high yields and using ecofriendly synthetic protocols. we highlight here the aromatic mbha, which have shown diverse biological activities as anti-leishmania chagasi and leishmania amazonen ...201222632793
hplc-based activity profiling for antiplasmodial compounds in the traditional indonesian medicinal plant carica papaya l.leaf decoctions of carica papaya have been traditionally used in some parts of indonesia to treat and prevent malaria. leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo.201424892830
synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.importance of heme in african trypanosomes, leishmania sp. and plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. consequently, twenty-four porphyrin precursors and derivatives were evaluated against leishmania donovani, trypanosoma brucei and plasmodium sp. the best active compound against trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, wit ...201323851117
amino acid, dipeptide and pseudodipeptide conjugates of ring-substituted 8-aminoquinolines: synthesis and evaluation of anti-infective, β-haematin inhibition and cytotoxic activities.three new series of 8-aminoquinolines with modifications in the side-chain by conjugation with amino acids, dipeptides and pseudodipeptides have been synthesized. the synthesized compounds were tested for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant plasmodium falciparum strains, in vitro cytotoxicity in mammalian kidney cells (vero), in vitro antileishmanial activity against leishmania donovani, in vitro antimicrobial activity and in vitro inhibition of ...201222483965
design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents.in this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. the compounds were rationalized basing on docking studies of the dihydrofolate reductase (dhfr from trypanosoma cruzi, leishmania major and plasmodium vivax) and pteridin reductase (ptr from t. cruzi and l. major) structures. all compounds were in vitro screened against both bloodstream trypomastigotes of ...201525899334
endogenous mouse mammary tumor viruses (mtv): new roles for an old virus in cancer, infection, and immunity.mouse mammary tumor viruses are beta-retroviruses that exist in both exogenous (mmtv) and endogenous (mtv) forms. exogenous mmtv is transmitted via the milk of lactating animals and is capable of inducing mammary gland tumors later in life. mmtv has provided a number of critical models for studying both viral infection as well as human breast cancer. in addition to the horizontally transmitted mmtv, most inbred mouse strains contain permanently integrated mtv proviruses within their genome that ...201324324930
antiparasitic activities of two sesquiterpenic lactones isolated from acanthospermum hispidum d.c.aerial parts of acanthospermum hispidum d.c. are often used by traditional healers in benin for various diseases and especially for malaria.201222440261
activation and exhaustion of antigen-specific cd8(+) t cells occur in different splenic compartments during infection with plasmodium berghei.the spleen is the major organ in which t cells are primed during infection with malaria parasites. however, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. we examined murine cd8(+) t cell responses during infection with plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (ova) protein and compared the responses with those elicited by listeria monocytogenes expressing the sam ...201728163249
development of memory cd8+ t cells and their recall responses during blood-stage infection with plasmodium berghei anka.conditions required for establishing protective immune memory vary depending on the infecting microbe. although the memory immune response against malaria infection is generally thought to be relatively slow to develop and can be lost rapidly, experimental evidence is insufficient. in this report, we investigated the generation, maintenance, and recall responses of ag-specific memory cd8(+) t cells using plasmodium berghei anka expressing ova (pba-ova) as a model system. mice were transferred wi ...201223008449
the mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.a wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. hence observation of these regions has wide application to understanding host-pathogen interactions. interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with ...201728351758
evaluation of plasmodium vivax cell-traversal protein for ookinetes and sporozoites as a preerythrocytic p. vivax vaccine.four different vaccine platforms, each targeting the human malaria parasite plasmodium vivax cell-traversal protein for ookinetes and sporozoites (pvceltos), were generated and assessed for protective efficacy. these platforms consisted of a recombinant chimpanzee adenoviral vector 63 (chad63) expressing pvceltos (ad), a recombinant modified vaccinia virus ankara expressing pvceltos (mva), pvceltos conjugated to bacteriophage qβ virus-like particles (vlps), and a recombinant pvceltos protein exp ...201728179403
an experimental model to study tuberculosis-malaria coinfection upon natural transmission of mycobacterium tuberculosis and plasmodium berghei.coinfections naturally occur due to the geographic overlap of distinct types of pathogenic organisms. concurrent infections most likely modulate the respective immune response to each single pathogen and may thereby affect pathogenesis and disease outcome. coinfected patients may also respond differentially to anti-infective interventions. coinfection between tuberculosis as caused by mycobacteria and the malaria parasite plasmodium, both of which are coendemic in many parts of sub-saharan afric ...201424637905
irf8-regulated genomic responses drive pathological inflammation during cerebral malaria.interferon regulatory factor 8 (irf8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. bxh2 mice harbor a severely hypomorphic allele at irf8 (irf8(r294c)) that causes susceptibility to infection with intracellular pathogens including mycobacterium tuberculosis. we report that bxh2 are completely resistant to the development of cerebral malaria (ecm) following plasmodium berghei anka infection. comparative transcriptional profiling of brain rna ...201323853600
controlled release of artemisone for the treatment of experimental cerebral malaria.cerebral malaria (cm) is a leading cause of malarial mortality resulting from infection by plasmodium falciparum. treatment commonly involves adjunctive care and injections or transfusion of artemisinins. all artemisinins that are in current use are metabolized to dihydroxyartemisinin (dha), to which there is already some parasite resistance. we used artemisone, a derivative that does not convert to dha, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an ...201728249591
myeloid expression of the ap-1 transcription factor junb modulates outcomes of type 1 and type 2 parasitic infections.activation of macrophages is a key step in the initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. it was recently shown that the ap-1 family transcription factor junb positively regulates macrophage activation in response to toll-like receptor agonists that promote classical or m1 polarization, as well as to the cytokine interleukin-4 (il-4), which elicits an alternatively activated or m2 phenotype. howeve ...201526178310
transient expression of plasmodium berghei msp8 and hap2 in the marine protozoan parasite perkinsus marinus.perkinsus marinus is a protozoan parasite of molluscs that can be propagated in vitro in a defined culture medium, in the absence of host cells. we previously reported that p. marinus trophozoites can be transfected with high efficiency by electroporation using a plasmid based on moe, a highly expressed gene, and proposed its potential use as a "pseudoparasite." this is a novel gene expression platform for parasites of medical relevance for which the choice of the surrogate organism is based on ...201727723436
evidence of cross-stage cd8+ t cell epitopes in malaria pre-erythrocytic and blood stage infections.malaria parasites have a complex, multi-stage life cycle, and there is a widely held view that each stage displays a distinct set of antigens presented to the immune system. yet, molecular analysis of malaria parasites suggests that many putative antigenic targets are shared amongst the different stages. the specificities of these cross-stage antigens and the functions of the immune responses they elicit are poorly characterised. it is well known that cd8+ t cells play opposing immune functions ...201728380250
a novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions.transmission-blocking interventions (tbis) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. tbis include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. accurate methodologies are key to assess tbi efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. measuring intervention e ...201728376897
phylogenetic profiles of all membrane transport proteins.in order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. proteins that are essential to survival and specific to malaria parasites are key candidates. to survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. membrane transport proteins mediate all ...201628357319
anopheles stephensi heme peroxidase hpx15 suppresses midgut immunity to support plasmodium development.the heme peroxidase hpx15 is an evolutionary conserved anopheline lineage-specific gene. previously, we found that this gene is present in the genome of 19 worldwide distributed different species of anopheles mosquito and its orthologs are absent in other mosquitoes, insects, or human. in addition, 65-99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. in this study, we found that ...201728352267
plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites.cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. here, we show that the apicomplexan parasites toxoplasma gondii and plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. cytokinins regulate the growth and cell cycle progression of t. gondii by mediating expression of the cyclin gene tgcyc4. ...201728344153
extended protection capabilities of an immature dendritic-cell targeting malaria sporozoite vaccine.mouse studies evaluating candidate malaria vaccines have typically examined protective efficacy over the relatively short time frames of several weeks after the final of multiple immunizations. the current study examines the protective ability in a mouse model system of a novel protein vaccine construct in which the adjuvant polyinosinic polycytidilic acid (poly(i:c)) is used in combination with a vaccine in which the immature dendritic cell targeting chemokine, macrophage inflammatory protein 3 ...201728342669
the maternally inheritable wolbachia walbb induces refractoriness to plasmodium berghei in anopheles stephensi.the endosymbiont wolbachia walbb induces refractoriness to plasmodium falciparum in anopheles stephensi, the primary mosquito vector of human malaria in the middle east and south asia. however, it remains unknown whether such refractoriness can be extended to other malaria species. in particular, it was reported that under very specific conditions, walbb can enhance plasmodium infection in some hosts. here, we measured the impact of walbb on the rodent malaria parasite plasmodium berghei in a. s ...201728337184
oxidative stress and genes regulation of cerebral malaria upon zizyphus spina-christi treatment in a murine model.the development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. the urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. interestingly, the zizyphus spina cristi leaf extract (zle) has been found to exhibit antiplasmodial activity. this study evaluated the protective effect of zle against plasmodium berghei-induced cerebral ...201728336326
effects of artesunate on some biochemical parameters in pregnant albino wistar rats challenged with lethal strain plasmodium berghei nk65: appreciating the activities of artemisinin drugs on key pregnancy hormone balance.in humans, malaria in pregnancy can cause serious maternal and foetal morbidity and in extreme untreated cases, foetal mortality occurs. the therapeutic approach to curbing this malaise is the administration of an effective and/or combinations of anti-malaria medicaments. acute or chronic administration of some of these drugs, however, gives rise to some adverse medical conditions including reproductive dysfunction, especially in pregnancy. studies aimed at the hormonal interplays following admi ...201728336173
antimalarial and antiplasmodial activity of husk extract and fractions of zea mays.zea mays l. (poacae) husk decoctions are traditionally used in the treatment of malaria by various tribes in nigeria.201728320254
docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.a series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of plasmodium berghei. the compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant w2 strain of plasmodium falciparum and β-haematin inhibition studies. all the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. twelve out of fifteen com ...201728318947
immunophenotyping of blood mononuclear cells from p. berghei (nk-65) infected and immunized balb/c mice.the present study demonstrates the alterations in the frequencies of helper, cytotoxic and suppressor t cells in blood of p. berghei infected and tpa immunized rodent host towards the induction of protective immune response. statistically significant (p < 0.005) number of cd4(+) t cells was recorded on d9 [post challenge (pc)] meanwhile cd4(+) treg cells were found to be declined in immunized mice as compared to infected. this increase in frequencies of t helper cells points towards the stimulat ...201728316421
Displaying items 4701 - 4800 of 5568