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transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito, aedes aegypti.controlled sex-, stage- and tissue-specific expression of antipathogen effector molecules is important for genetic engineering strategies to control mosquito-borne diseases. adult female salivary glands are involved in pathogen transmission to human hosts and are target sites for expression of antipathogen effector molecules. the aedes aegypti 30k a and 30k b genes are expressed exclusively in adult female salivary glands and are transcribed divergently from start sites separated by 263 nucleoti ...201020738425
production of a transgenic mosquito expressing circumsporozoite protein, a malarial protein, in the salivary gland of anopheles stephensi (diptera: culicidae).we are producing a transgenic mosquito, a flying syringe, to deliver a vaccine protein to human beings via the saliva the mosquito deposits in the skin while biting. the mosquito produces a vaccine protein in the salivary gland (sg) and deposits the protein into the host's skin when it takes the host's blood. we chose circumsporozoite protein (csp), currently the most promising malaria vaccine candidate, to be expressed in the sg of anopheles stephensi. to transform the mosquitoes, plasmid conta ...201020802540
replacing adenoviral vector hvr1 with a malaria b cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice.although adenovirus (ad) has been regarded as an excellent vaccine vector, there are 2 major drawbacks to using this platform: (a) ad-based vaccines induce a relatively weak humoral response against encoded transgenes, and (b) preexisting immunity to ad is highly prevalent among the general population. to overcome these obstacles, we constructed an ad-based malaria vaccine by inserting a b cell epitope derived from a plasmodium yoelii circumsporozoite (cs) protein (referred to as the pycs-b epit ...201020811151
multiple antigen peptide vaccines against plasmodium falciparum malaria.the multiple antigen peptide (map) approach is an effective method to chemically synthesize and deliver multiple t-cell and b-cell epitopes as the constituents of a single immunogen. here we report on the design, chemical synthesis, and immunogenicity of three plasmodium falciparum map vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. antibody and cellular responses were determined in three inbred (c57bl/6, balb/c, and a/j) strains, one ...201020823210
naturally occurring triggers that induce apoptosis-like programmed cell death in plasmodium berghei ookinetes.several protozoan parasites have been shown to undergo a form of programmed cell death that exhibits morphological features associated with metazoan apoptosis. these include the rodent malaria parasite, plasmodium berghei. malaria zygotes develop in the mosquito midgut lumen, forming motile ookinetes. up to 50% of these exhibit phenotypic markers of apoptosis; as do those grown in culture. we hypothesised that naturally occurring signals induce many ookinetes to undergo apoptosis before midgut t ...201020844583
experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites.classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisini ...201020846421
central carbon metabolism of plasmodium parasites.the central role of metabolic perturbation to the pathology of malaria, the promise of antimetabolites as antimalarial drugs and a basic scientific interest in understanding this fascinating example of highly divergent microbial metabolism has spurred a major and concerted research effort towards elucidating the metabolic network of the plasmodium parasites. central carbon metabolism, broadly comprising the flow of carbon from nutrients into biomass, has been a particular focus due to clear and ...201120849882
molecular evidence for multiple infections as revealed by typing of asaia bacterial symbionts of four mosquito species.the recent increased detection of acetic acid bacteria (aab) of the genus asaia as symbionts of mosquitoes, such as anopheles spp. and aedes spp., prompted us to investigate the diversity of these symbionts and their relationships in different mosquito species and populations. following cultivation-dependent and -independent techniques, we investigated the microbiota associated with four mosquito species, anopheles stephensi, anopheles gambiae, aedes aegypti, and aedes albopictus, which are impo ...201020851960
molecular genetics evidence for the in vivo roles of the two major nadph-dependent disulfide reductases in the malaria parasite.malaria-associated pathology is caused by the continuous expansion of plasmodium parasites inside host erythrocytes. to maintain a reducing intracellular milieu in an oxygen-rich environment, malaria parasites have evolved a complex antioxidative network based on two central electron donors, glutathione and thioredoxin. here, we dissected the in vivo roles of both redox pathways by gene targeting of the respective nadph-dependent disulfide reductases. we show that plasmodium berghei glutathione ...201020852334
2-hexadecynoic acid inhibits plasmodial fas-ii enzymes and arrests erythrocytic and liver stage plasmodium infections.acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. in this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (hdas) and evaluated their in vitro activity against erythrocytic (blood) stages of plasmodium falciparum and liver stages of plasmodium yoelii infections. since the type ii fatty acid biosynthesis pathway (pffas-ii) has recently been shown to be indispensable for liver stage malaria parasites, t ...201020855214
constitutive activation of the midgut response to bacillus thuringiensis in bt-resistant spodoptera exigua.bacillus thuringiensis is the most effective microbial control agent for controlling numerous species from different insect orders. the main threat for the long term use of b. thuringiensis in pest control is the ability of insects to develop resistance. thus, the identification of insect genes involved in conferring resistance is of paramount importance. a colony of spodoptera exigua (lepidoptera: noctuidae) was selected for 15 years in the laboratory for resistance to xentari™, a b. thuringien ...201020862260
infection of anopheles gambiae mosquitoes with entomopathogenic fungi: effect of host age and blood-feeding status.physiological characteristics of insects can influence their susceptibility to fungal infection of which age and nutritional status are among the most important. an understanding of host-pathogen interaction with respect to these physiological characteristics of the host is essential if we are to develop fungal formulations capable of reducing malaria transmission under field conditions. here, two independent bioassays were conducted to study the effect of age and blood-feeding status on fungal ...201020872014
development of the malaria parasite in the skin of the mammalian host.the first step of plasmodium development in vertebrates is the transformation of the sporozoite, the parasite stage injected by the mosquito in the skin, into merozoites, the stage that invades erythrocytes and initiates the disease. the current view is that, in mammals, this stage conversion occurs only inside hepatocytes. here, we document the transformation of sporozoites of rodent-infecting plasmodium into merozoites in the skin of mice. after mosquito bite, ∼50% of the parasites remain in t ...201020921402
larvicidal activity of metabolites from the endophytic podospora sp. against the malaria vector anopheles gambiae.in a screening for natural products with mosquito larvicidal activities, the endophytic fungus podospora sp. isolated from the plant laggera alata (asteraceae) was conspicuous. two xanthones, sterigmatocystin (1) and secosterigmatocystin (2), and an anthraquinone derivative (3) 13-hydroxyversicolorin b were isolated after fermentation on m(2) medium. these compounds were characterised using spectroscopic and x-ray analysis and examined against third instar larvae of anopheles gambiae. the result ...201020922412
past, present and future research directions with pichia anomala.the first international pichia anomala symposium provided a survey of past, recent and ongoing research on this yeast. the research community working with this yeast has focussed on several areas. based on molecular data, a revision of the taxonomy is required: the name p. anomala is no longer applicable, as the genus pichia is polyphyletic. the current debate centres on whether the yeast should be designated as wickerhamomyces anomalus or if the previous name, hansenula anomala, should be re-in ...201020924674
plasmodium ovale infection in malaysia: first imported case.plasmodium ovale infection is rarely reported in malaysia. this is the first imported case of p. ovale infection in malaysia which was initially misdiagnosed as plasmodium vivax.201020929588
reproduction-longevity trade-off in anopheles gambiae (diptera: culicidae).reduced survival and future reproduction due to of current reproduction is a trade-off known as the cost of reproduction. surprisingly, only a few studies have assessed the cost of reproduction in arthropod disease vectors, despite its effect on longevity, and thus on vectorial capacity. we evaluated the cost of reproduction on survival of anopheles gambiae giles by comparing mosquitoes that were denied exposure to the other sex, hereafter named virgins, and those that were allowed exposure to t ...201020939369
the systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission.although eukaryotic protein kinases (epks) contribute to many cellular processes, only three plasmodium falciparum epks have thus far been identified as essential for parasite asexual blood stage development. to identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of epks in the genetically tractable rodent parasite plasmodium berghei. modeling domain signatures of conventional epks identified 66 put ...201020951971
a kunitz protease inhibitor from dermacentor variabilis, a vector for spotted fever group rickettsiae, limits rickettsia montanensis invasion.a defining facet of tick-rickettsia symbioses is the molecular strategy employed by each partner to ensure its own survival. ticks must control rickettsial colonization to avoid immediate death. in the current study, we show that rickettsial abundance in the tick midgut increases once the expression of a kunitz-type serine protease inhibitor from the american dog tick (dermacentor variabilis) (dvkpi) is suppressed by small interfering rna (sirna). a series of in vitro invasion assays suggested t ...201020956566
larvicidal efficacy of medicinal plant extracts against anopheles stephensi and culex quinquefasciatus (diptera: culicidae).mosquitoes transmit serious human diseases, causing millions of deaths every year. natural products of plant origin with insecticidal properties have been used in recent years for control of a variety of pest insects and vectors. the present study was based on assessments of the larvicidal activity to determine the efficacies of hexane, chloroform, ethyl acetate, acetone and methanol extracts of ten medicinal plants tested against fourth instar larvae of malaria vector, anopheles stephensi listo ...201020962718
evaluation of selected south african ethnomedicinal plants as mosquito repellents against the anopheles arabiensis mosquito in a rodent model.this study was initiated to establish whether any south african ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito repellent properties.201021029442
the small gtpase rheb is a key component linking amino acid signaling and tor in the nutritional pathway that controls mosquito egg development.mosquitoes transmit numerous devastating human diseases because they require blood feeding for egg development. previously, we have shown that the nutritional target-of-rapamycin (tor) pathway mediates blood-meal activation of mosquito reproductive cycles. blood-derived amino acid (aa) signaling through the nutrient-sensitive tor kinase is critical for the transcriptional activation of the major yolk protein precursor (ypp) gene, vitellogenin (vg), initiation of vitellogenesis and egg developmen ...201021035549
ranking of elimination feasibility between malaria-endemic countries.experience gained from the global malaria eradication program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. the analysis was done separately for plasmodium falciparum and plasmodium vivax, and the li ...201021035838
a physical map for an asian malaria mosquito, anopheles stephensi.physical mapping is a useful approach for studying genome organization and evolution as well as for genome sequence assembly. the availability of polytene chromosomes in malaria mosquitoes provides a unique opportunity to develop high-resolution physical maps. we report a 0.6-mb-resolution physical map consisting of 422 dna markers hybridized to 379 chromosomal sites of the anopheles stephensi polytene chromosomes. this makes an. stephensi second only to anopheles gambiae in density of a physica ...201021036831
plasmodium falciparum malaria challenge by the bite of aseptic anopheles stephensi mosquitoes: results of a randomized infectivity trial.experimental infection of malaria-naïve volunteers by the bite of plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. the standard model relies on the bite of five infected mosquitoes to induce malaria. we examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current good manufacturing practices (cgmps).201021042404
odorant-binding proteins of the malaria mosquito anopheles funestus sensu stricto.the mosquito anopheles funestus is one of the major malaria vector species in sub-saharan africa. olfaction is essential in guiding mosquito behaviors. odorant-binding proteins (obps) are highly expressed in insect olfactory tissues and involved in the first step of odorant reception. an improved understanding of the function of malaria mosquito obps may contribute to identifying new attractants/repellents and assist in the development of more efficient and environmentally friendly mosquito cont ...201021042539
pseudoxanthomonas icgebensis sp. nov., isolated from the midgut of anopheles stephensi field-collected larvae.a gram-negative, aerobic, golden yellow, rod-shaped bacterium, a strain designated icgeb-l15(t), was isolated from the larval midgut of anopheles stephensi captured in district jhajjar, haryana, india. the strain icgeb-l15(t) grows at 30-50°c (optimum 30-37°c), ph 6.5-8.5 (optimum 7.0-8.0) and in the presence of 2% nacl. the major fatty acids were iso-c(15:0) (22.5% of total fatty acid), anteiso-c(15:0) (16.5%), iso-c(17:1) 9c (10.3%), iso-c(16:0) (7.3%), c(16:0) (6.1%), and iso-c(11:0) (5.3%). ...201021046337
identification and characterization of a liver stage-specific promoter region of the malaria parasite plasmodium.during the blood meal of a plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. the plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel t ...201021048918
population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions.the combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. in a malaria model system, it has been shown that the progression of plasmodium berghei through anopheles stephensi and the survival of the mosquito both depend non-linearly on parasite density. these processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (tbis) ...201021050427
detection of 1014f kdr mutation in four major anopheline malaria vectors in indonesia.malaria is a serious public health problem in indonesia, particularly in areas outside java and bali. the spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. to better understand patterns of transmission and resistance in indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, purworejo in central java, south lampung district in sumatera an ...201021054903
insight into the salivary transcriptome and proteome of dipetalogaster maxima.dipetalogaster maxima is a blood-sucking hemiptera that inhabits sylvatic areas in mexico. it usually takes its blood meal from lizards, but following human population growth, it invaded suburban areas, feeding also on humans and domestic animals. hematophagous insect salivary glands produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. to obtain further insight into the salivary biochemical and pharmacologic com ...201121058630
malaria imc1 membrane skeleton proteins operate autonomously and participate in motility independently of cell shape.plasmodium imc1 (inner membrane complex 1) proteins comprise components of the subpellicular network, a lattice of intermediate filaments that form a structural part of the pellicle in the zoite stages of malaria parasites. family members imc1a and imc1b are differentially expressed in sporozoites and ookinetes, respectively, but have functionally equivalent roles affecting cell morphology, strength, motility, and infectivity. because of the coincident effects of previous imc1 gene disruptions o ...201021098480
efficacy of an insecticide paint against insecticide-susceptible and resistant mosquitoes - part 1: laboratory evaluation.the main malaria vector anopheles gambiae and the urban pest nuisance culex quinquefasciatus are increasingly resistant to pyrethroids in many african countries. there is a need for new products and strategies. insecticide paint inesfly 5a igr™, containing two organophosphates (ops), chlorpyrifos and diazinon, and insect growth regulator (igr), pyriproxyfen, was tested under laboratory conditions for 12 months following whopes phase i procedures.201021108819
effects of plasmodium gallinaceum on hemolymph physiology of aedes aegypti during parasite development.insect disease vectors show diminished fecundity when infected with plasmodium. this phenomenon has already been demonstrated in laboratory models such as aedes aegypti, anopheles gambiae and anopheles stephensi. this study demonstrates several changes in physiological processes of a. aegypti occurring upon infection with plasmodium gallinaceum, such as reduced ecdysteroid levels in hemolymph as well as altered expression patterns for genes involved in vitellogenesis, lipid transport and immune ...201021112329
microrna mir-275 is indispensable for blood digestion and egg development in the mosquito aedes aegypti.the mosquito aedes aegypti is the major vector of arboviral diseases, particularly of dengue fever, of which there are more than 100 million cases annually. mosquitoes, such as a. aegypti, serve as vectors for disease pathogens because they require vertebrate blood for their egg production. pathogen transmission is tightly linked to repeated cycles of obligatory blood feeding and egg maturation. thus, the understanding of mechanisms governing egg production is necessary to develop approaches tha ...201021115818
reactive oxygen species-dependent cell signaling regulates the mosquito immune response to plasmodium falciparum.reactive oxygen species (ros) have been implicated in direct killing of pathogens, increased tissue damage, and regulation of immune signaling pathways in mammalian cells. available research suggests that analogous phenomena affect the establishment of plasmodium infection in anopheles mosquitoes. we have previously shown that provision of human insulin in a blood meal leads to increased ros levels in anopheles stephensi. here, we demonstrate that provision of human insulin significantly increas ...201121126166
nonspecific patterns of vector, host and avian malaria parasite associations in a central african rainforest.malaria parasites use vertebrate hosts for asexual multiplication and culicidae mosquitoes for sexual and asexual development, yet the literature on avian malaria remains biased towards examining the asexual stages of the life cycle in birds. to fully understand parasite evolution and mechanism of malaria transmission, knowledge of all three components of the vector-host-parasite system is essential. little is known about avian parasite-vector associations in african rainforests where numerous s ...201021134011
the function and three-dimensional structure of a thromboxane a2/cysteinyl leukotriene-binding protein from the saliva of a mosquito vector of the malaria parasite.the highly expressed d7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (cyslts). in this study we demonstrate that anst-d7l1, a two-domain member of this group from anopheles stephensi, retains the cyslt binding function seen in the homolog aed7 from aedes aegypti but has lost the ability to bind biogenic amines. unlike any previously characterized members of the d7 family, anst-d7l1 h ...201021152418
intradermal immunization of mice with radiation-attenuated sporozoites of plasmodium yoelii induces effective protective immunity.intravenous injection of mice with attenuated plasmodium berghei sporozoites induces sterile immunity to challenge with viable sporozoites. non-intravenous routes have been reported to yield poor immunity. because intravenous immunization has been considered to be unacceptable for large scale vaccination of humans, assessment was made of the results of intradermal immunization of mice with plasmodium yoelii, a rodent malaria parasite whose infectivity resembles that of human malaria.201021159170
a constitutive pan-hexose permease for the plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.glucose is considered essential for erythrocytic stages of the malaria parasite, plasmodium falciparum. importance of sugar and its permease for hepatic and sexual stages of plasmodium, however, remains elusive. moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. here, we reveal that hexose transporter 1 (ht1) of plasmodium berghei can transport glucose (k(m)~87 μm), mannose (k(i)~93 μm), fructose (k(i)~0.54 mm), and galactose (k(i)~5 mm) in l ...201021169382
malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut.physical contact is important for the interaction between animal cells, but it can represent a major challenge for protists like malaria parasites. recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. nanotubes represent small dynamic membranous extensions that consist of f-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication. ...201021173797
drosophila melanogaster as a model for human intestinal infection and pathology.recent findings concerning drosophila melanogaster intestinal pathology suggest that this model is well suited for the study of intestinal stem cell physiology during aging, stress and infection. despite the physiological divergence between vertebrates and insects, the modeling of human intestinal diseases is possible in drosophila because of the high degree of conservation between drosophila and mammals with respect to the signaling pathways that control intestinal development, regeneration and ...201121183483
bacterial endosymbiont localization in hyalesthes obsoletus, the insect vector of bois noir in vitis vinifera.one emerging disease of grapevine in europe is bois noir (bn), a phytoplasmosis caused by "candidatus phytoplasma solani" and spread in vineyards by the planthopper hyalesthes obsoletus (hemiptera: cixiidae). here we present the first full characterization of the bacterial community of this important disease vector collected from bn-contaminated areas in piedmont, italy. length heterogeneity pcr and denaturing gradient gel electrophoresis analysis targeting the 16s rrna gene revealed the presenc ...201021183640
strain-specific immunity induced by immunization with pre-erythrocytic stages of plasmodium chabaudi.one of the most promising approaches in the efforts to produce a malaria vaccine involves the use of attenuated whole sporozoite immunizations. attenuation may be achieved by the use of genetic modification, irradiation, chemical attenuation, or by the contemporaneous administration of antimalarial drugs that target only the erythrocytic stages of the parasite. most research to date has focused on the efficacy of these approaches upon challenge with parasites homologous to those used for the ini ...201121189655
insecticide resistance and malaria transmission: infection rate and oocyst burden in culex pipiens mosquitoes infected with plasmodium relictum.the control of most vectors of malaria is threatened by the spread of insecticide resistance. one factor that has been hitherto largely overlooked is the potential effects of insecticide resistance on the ability of mosquitoes to transmit malaria: are insecticide-resistant mosquitoes as good vectors of plasmodium as susceptible ones? the drastic physiological changes that accompany the evolution of insecticide resistance may indeed alter the ability of vectors to transmit diseases, a possibility ...201021194433
adenovirus particles that display the plasmodium falciparum circumsporozoite protein nanp repeat induce sporozoite-neutralizing antibodies in mice.adenovirus particles can be engineered to display exogenous peptides on their surfaces by modification of viral capsid proteins, and particles that display pathogen-derived peptides can induce protective immunity. we constructed viable recombinant adenoviruses that display b-cell epitopes from the plasmodium falciparum circumsporozoite protein (pfcsp) in the major adenovirus capsid protein, hexon. recombinants induced high-titer antibodies against csp when injected intraperitoneally into mice. s ...201121199707
transfection and mutagenesis of target genes in mosquito cells by locked nucleic acid-modified oligonucleotides.plasmodium parasites, the causative agent of malaria, are transmitted through the bites of infected anopheles mosquitoes resulting in over 250 million new infections each year. despite decades of research, there is still no vaccine against malaria, highlighting the need for novel control strategies. one innovative approach is the use of genetically modified mosquitoes to effectively control malaria parasite transmission. deliberate alterations of cell signaling pathways in the mosquito, via targ ...201021206476
the yeast wickerhamomyces anomalus (pichia anomala) inhabits the midgut and reproductive system of the asian malaria vector anopheles stephensi.while symbiosis between bacteria and insects has been thoroughly investigated in the last two decades, investments on the study of yeasts associated with insects have been limited. insect-associated yeasts are placed on different branches of the phylogenetic tree of fungi, indicating that these associations evolved independently on several occasions. isolation of yeasts is frequently reported from insect habitats, and in some cases yeasts have been detected in the insect gut and in other organs/ ...201121208355
cd4+ t cells modulate expansion and survival but not functional properties of effector and memory cd8+ t cells induced by malaria sporozoites.cd4(+) helper t cells are critical orchestrators of immune responses to infection and vaccination. during primary responses, naïve cd8(+) t cells may need "cd4 help" for optimal development of memory populations. the immunological factors attributed to cd4 help depend on the context of immunization and vary depending on the priming system. in response to immunization with radiation-attenuated plasmodium yoelii sporozoites, cd8(+) t cells in balb/c mice fail to generate large numbers of effector ...201121245909
protocol for production of a genetic cross of the rodent malaria parasites.variation in response to antimalarial drugs and in pathogenicity of malaria parasites is of biologic and medical importance. linkage mapping has led to successful identification of genes or loci underlying various traits in malaria parasites of rodents and humans. the malaria parasite plasmodium yoelii is one of many malaria species isolated from wild african rodents and has been adapted to grow in laboratories. this species reproduces many of the biologic characteristics of the human malaria pa ...201121248692
design of anti-parasitic and anti-fungal hydroxy-naphthoquinones that are less susceptible to drug resistance.atovaquone is a hydroxy-naphthoquinone that is used to treat parasitic and fungal infections including plasmodium falciparum (malaria), pneumocystis jivorecii (pneumonia) and toxoplasma gondii (toxoplasmosis). it blocks mitochondrial oxidation of ubiquinol in these organisms by binding to the ubiquinol oxidation site of the cytochrome bc(1) complex. failure of atovaquone treatment has been linked to the appearance of mutations in the mitochondrially encoded gene for cytochrome b. in order to det ...201121251932
plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase.plasmodium falciparum sporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. shortly after hepatocyte invasion, the parasite starts to produce liver stage antigen-1 (lsa-1), which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. the lsa-1 protein has been described as a flocculent mass, but its role in parasite devel ...201121255444
the malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host.plasmodium sporozoites make a remarkable journey from the mosquito midgut to the mammalian liver. the sporozoite's major surface protein, circumsporozoite protein (csp), is a multifunctional protein required for sporozoite development and likely mediates several steps of this journey. in this study, we show that csp has two conformational states, an adhesive conformation in which the c-terminal cell-adhesive domain is exposed and a nonadhesive conformation in which the n terminus masks this doma ...201121262960
molecular cloning, characterization, and expression analysis of an estrogen receptor-related receptor homologue in the cricket, teleogryllus emma.the estrogen receptor-related receptors (errs) are a group of nuclear receptors that were originally identified on the basis of sequence similarity to estrogen receptors. the three mammalian err genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, but the function and regulation of errs in invertebrates are not well understood. a homologue of human err was isolated from the cricket teleogryllus emma (ohmachi and matsumur ...201021265615
chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors.malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. in the present study, chlorfenapyr was evaluated against anopheles culicifacies and anopheles stephensi for its possible use in vector control.201121266037
site-specific integration and expression of an anti-malarial gene in transgenic anopheles gambiae significantly reduces plasmodium infections.diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. to circumvent these limitati ...201121283619
evidence that mutant pfcrt facilitates the transmission to mosquitoes of chloroquine-treated plasmodium gametocytes.resistance of the human malarial parasite plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. to test the hypothesis that the primary chloroquine resistance determinant, mutations in pfcrt, facilitates parasite transmission under drug pressure, we have i ...201121288823
development of a new version of the liverpool malaria model. i. refining the parameter settings and mathematical formulation of basic processes based on a literature review.a warm and humid climate triggers several water-associated diseases such as malaria. climate- or weather-driven malaria models, therefore, allow for a better understanding of malaria transmission dynamics. the liverpool malaria model (lmm) is a mathematical-biological model of malaria parasite dynamics using daily temperature and precipitation data. in this study, the parameter settings of the lmm are refined and a new mathematical formulation of key processes related to the growth and size of t ...201121314922
mosquito larvicidal, ovicidal, and repellent properties of botanical extracts against anopheles stephensi, aedes aegypti, and culex quinquefasciatus (diptera: culicidae).mosquito-borne diseases have an economic impact, including loss in commercial and labor outputs, particularly in countries with tropical and subtropical climates; however, no part of the world is free from vector-borne diseases. in mosquito control programs, botanical origin may have the potential to be used successfully as eggs, larvae, and adult. the larvicidal, ovicidal, and repellent activities of crude benzene and ethyl acetate extracts of leaf of ervatamia coronaria and caesalpinia pulcher ...201121318385
energy metabolism affects susceptibility of anopheles gambiae mosquitoes to plasmodium infection.previous studies showed that anopheles gambiae l3-5 females, which are refractory (r) to plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (s) g3 females. our studies revealed that r females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. furthermore, ...201121320598
analysis of two novel midgut-specific promoters driving transgene expression in anopheles stephensi mosquitoes.tissue-specific promoters controlling the expression of transgenes in anopheles mosquitoes represent a valuable tool both for studying the interaction between these malaria vectors and the plasmodium parasites they transmit and for novel malaria control strategies based on developing plasmodium-refractory mosquitoes by expressing anti-parasitic genes. with this aim we have studied the promoter regions of two genes from the most important malaria vector, anopheles gambiae, whose expression is str ...201121326609
development of metarhizium anisopliae and beauveria bassiana formulations for control of malaria mosquito larvae.the entomopathogenic fungi metarhizium anisopliae and beauveria bassiana have demonstrated effectiveness against anopheline larvae in the laboratory. however, utilising these fungi for the control of anopheline larvae under field conditions, relies on development of effective means of application as well as reducing their sensitivity to uv radiation, high temperatures and the inevitable contact with water. this study was conducted to develop formulations that facilitate the application of metarh ...201121342492
cutting edge: attrition of plasmodium-specific memory cd8 t cells results in decreased protection that is rescued by booster immunization.sterile protection against infection with plasmodium sporozoites requires high numbers of memory cd8 t cells. however, infections with unrelated pathogens, as may occur in areas endemic to malaria, can dramatically decrease pre-existing memory cd8 t cells. it remains unknown whether unrelated infections will compromise numbers of plasmodium-specific memory cd8 t cells and thus limit the duration of antimalarial immunity generated by subunit vaccination. we show that p. berghei circumsporozoite-s ...201121357257
inhibitory effect of tnf-+¦ on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.the liver stages of malaria parasites are inhibited by cytokines such as interferon-+¦ or interleukin (il)-6. binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (no) and radical oxygen intermediates (roi), which kill hepatic parasites. however, conflicting results were obtained with tnf-+¦ possibly because of differences in the models used. we have reassessed the role of tnf-+¦ in the different cellular systems used to ...201121394207
anopheles stephensi saliva enhances progression of cerebral malaria in a murine model.malaria accounts for the greatest morbidity and mortality of any arthropod-borne disease globally. recently, it was determined that the protective antisporozoite cd8+ t-cell response originates predominantly from cutaneous lymph nodes draining the site of parasite inoculation by an anopheles mosquito. the female mosquito inoculates sporozoites along with an assortment of salivary proteins into the skin of its mammalian host. mosquito saliva has demonstrable antihemostatic as well as various immu ...201121395422
use of a selective inhibitor to define the chemotherapeutic potential of the plasmodial hexose transporter in different stages of the parasite's life cycle.during blood infection, malarial parasites use d-glucose as their main energy source. the plasmodium falciparum hexose transporter (pfht), which mediates the uptake of d-glucose into parasites, is essential for survival of asexual blood-stage parasites. recently, genetic studies in the rodent malaria model, plasmodium berghei, found that the orthologous hexose transporter (pbht) is expressed throughout the parasite's development within the mosquito vector, in addition to being essential during i ...201121402842
reactive oxygen species scavenging by catalase is important for female lutzomyia longipalpis fecundity and mortality.the phlebotomine sand fly lutzomyia longipalpis is the most important vector of american visceral leishmaniasis (avl), the disseminated and most serious form of the disease in central and south america. in the natural environment, most female l. longipalpis are thought to survive for less than 10 days and will feed on blood only once or twice during their lifetime. successful transmission of parasites occurs when a leishmania-infected female sand fly feeds on a new host. knowledge of factors aff ...201121408075
identification of two new protective pre-erythrocytic malaria vaccine antigen candidates.despite years of effort, a licensed malaria vaccine is not yet available. one of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. to counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. since most of the malaria vaccine antigens that have been evaluated ...201121410955
humoral response to the anopheles gambiae salivary protein gsg6: a serological indicator of exposure to afrotropical malaria vectors.salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. however, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactivity to other antigens. toward the development of a serological marker of exposure to afrotropical malaria vectors we expressed the anopheles gambiae g ...201121437289
induction of antimalaria immunity by pyrimethamine prophylaxis during exposure to sporozoites is curtailed by parasite resistance.each year, infections with the protozoan parasite plasmodium falciparum kill 1 million people, mostly children in africa. intermittent preventive treatment (ipt) with sulfadoxine-pyrimethamine (sp) reduces the incidence of malaria and aims to prevent mortality in infants, children, and pregnant women. there is contradictory evidence as to whether this strategy may generate additional protection against reinfection beyond the limited duration of the intervention. previous work established that ab ...201121444698
prodigiosin produced by serratia marcescens nmcc46 as a mosquito larvicidal agent against aedes aegypti and anopheles stephensi.microbial control agents offer alternatives to chemical pest control as they can be more selective than chemical insecticides. the present study evaluates the mosquito larvicidal potential of microbial pigment prodigiosin produced by serratia marcescens nmcc46 against aedes aegypti and anopheles stephensi. the pigment of s. marcescens nmcc46 was extracted after 24 h from mannitol containing nutrient broth media. the effects of crude extracted pigment on the growth, survival, development, and oth ...201121451991
larvicidal potential of silver nanoparticles synthesized using fungus cochliobolus lunatus against aedes aegypti (linnaeus, 1762) and anopheles stephensi liston (diptera; culicidae).larvicides play a vital role in controlling mosquitoes in their breeding sites. the present study was carried out to establish the larvicidal activities of mycosynthesized silver nanoparticles (agnps) against vectors: aedes aegypti and anopheles stephensi responsible for diseases of public health importance. the agnps synthesized by filamentous fungus cochliobolus lunatus, characterized by uv-vis spectrophotometry, fourier transform infrared spectroscopy, x-ray diffraction, scanning electron mic ...201121451993
plasmodium cysteine repeat modular proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host.the plasmodium cysteine repeat modular proteins (pcrmp) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. analysis of mutants of the rodent parasite plasmodium berghei lacking expression of pcrmp1 or 2 showed that these proteins are essential for targeting of p. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse.201121453484
arm-specific dynamics of chromosome evolution in malaria mosquitoes.abstract:201121473772
frontiers in climate change-disease research.the notion that climate change will generally increase human and wildlife diseases has garnered considerable public attention, but remains controversial and seems inconsistent with the expectation that climate change will also cause parasite extinctions. in this review, we highlight the frontiers in climate change-infectious disease research by reviewing knowledge gaps that make this controversy difficult to resolve. we suggest that forecasts of climate-change impacts on disease can be improved ...201121481487
parasite killing in malaria non-vector mosquito anopheles culicifacies species b: implication of nitric oxide synthase upregulation.anopheles culicifacies, the main vector of human malaria in rural india, is a complex of five sibling species. despite being phylogenetically related, a naturally selected subgroup species b of this sibling species complex is found to be a poor vector of malaria. we have attempted to understand the differences between vector and non-vector anopheles culicifacies mosquitoes in terms of transcriptionally activated nitric oxide synthase (acnos) physiologies to elucidate the mechanism of refractorin ...201121483693
towards an in vitro model of plasmodium hypnozoites suitable for drug discovery.amongst the plasmodium species in humans, only p. vivax and p. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. relapses contribute to increased morbidity, and complicate malaria elimination programs. a single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. novel compounds are thus urgently ...201121483865
activation of the hypnozoite: a part of plasmodium vivax life cycle and survival.abstract:201121496287
a human phase i/iia malaria challenge trial of a polyprotein malaria vaccine.we examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, fp9-pp and mva-pp, expressing the same polyprotein consisting of six pre-erythrocytic antigens from plasmodium falciparum. following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. the vaccines were safe but interferon-γ elispot responses were low compared to oth ...201121501642
identification and distribution of a gaba receptor mutation conferring dieldrin resistance in the malaria vector anopheles funestus in africa.growing problems of pyrethroid resistance in anopheles funestus have intensified efforts to identify alternative insecticides. many agrochemicals target the gaba receptors, but cross-resistance from dieldrin resistance may preclude their introduction. dieldrin resistance was detected in an. funestus populations from west (burkina faso) and central (cameroon) africa, but populations from east (uganda) and southern africa (mozambique and malawi) were fully susceptible to this insecticide. partial ...201121501685
engineered resistance to plasmodium falciparum development in transgenic anopheles stephensi.transposon-mediated transformation was used to produce anopheles stephensi that express single-chain antibodies (scfvs) designed to target the human malaria parasite, plasmodium falciparum. the scfvs, m1c3, m4b7, and m2a10, are derived from mouse monoclonal antibodies that inhibit either ookinete invasion of the midgut or sporozoite invasion of salivary glands. the scfvs that target the parasite surface, m4b7 and m2a10, were fused to an anopheles gambiae antimicrobial peptide, cecropin a. previo ...201121533066
efficacy of advanced odomos repellent cream (n, n-diethyl-benzamide) against mosquito vectors.background & objectives : repellents are commonly used personal protection measures to avoid mosquito bites. in the present study, advanced odomos cream (12% n, n-diethyl-benzamide) was tested for its efficacy against mosquitoes in comparison to deet (n,n-diethyl-3-methyl benzamide). methods: bioassays were conducted to assess the repellency of advanced odomos and deet creams against anopheles stephensi and aedes aegypti. their efficacy was tested on human volunteers applied with different conce ...201121537097
plasmodium falciparum infection during suppressive prophylaxis with mefloquine does not induce an antibody response to merozoite surface protein-1(42).abstract. a sensitive biomarker of malaria infection would obviate the need for placebo control arms in clinical trials of malaria prophylactic drugs. antibodies to the 42-kda fragment of merozoite surface protein-1 (msp1(42)) have been identified as a potential marker of malaria exposure in individuals receiving prophylaxis with mefloquine. we conducted an open-label trial to determine the sensitivity of seroconversion to msp1(42), defined as a fourfold rise in enzyme-linked immunosorbant assay ...201121540397
seasonal abundance and host-feeding patterns of anopheline vectors in malaria endemic area of iran.seasonal abundance and tendency to feed on humans are important parameters to measure for effective control of malaria vectors. the objective of this study was to describe relation between feeding pattern, abundance, and resting behavior of four malaria vectors in southern iran. this study was conducted in ten indicator villages (based on malaria incidence and entomological indices) in mountainous/hilly and plain regions situated south and southeastern iran. mosquito vectors were collected from ...201021559055
disruption of the plasmodium falciparum liver stage antigen-1 locus causes a differentiation defect in late liver stage parasites.the malaria parasite plasmodium falciparum infects humans and first targets the liver where liver stage parasites undergo preerythrocytic replication. liver stage antigen-1 (lsa-1) is currently the only identified p. falciparum protein for which expression is restricted to liver stages. yet, the importance of lsa-1 for liver stage parasite development remains unknown. here we deleted lsa-1 in the nf54 strain of p. falciparum and analyzed the lsa-1(-) parasites throughout their life cycle. lsa-1( ...201121569184
the midgut transcriptome of phlebotomus (larroussius) perniciosus, a vector of leishmania infantum: comparison of sugar fed and blood fed sand flies.abstract:201121569254
host-mediated regulation of superinfection in malaria.in regions of high rates of malaria transmission, mosquitoes repeatedly transmit liver-tropic plasmodium sporozoites to individuals who already have blood-stage parasitemia. this manifests itself in semi-immune children (who have been exposed since birth to plasmodium infection and as such show low levels of peripheral parasitemia but can still be infected) older than 5 years of age by concurrent carriage of different parasite genotypes at low asymptomatic parasitemias. superinfection presents a ...201121572427
a new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in anopheles mosquitoes.plasmodium requires an obligatory life stage in its mosquito host. the parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.201121573077
laboratory selection for an accelerated mosquito sexual development rate.abstract: background: separating males and females at the early adult stage did not ensure the virginity of females of anopheles arabiensis (dongola laboratory strain), whereas two years earlier this method had been successful. in most mosquito species, newly emerged males and females are not able to mate successfully. for anopheline species, a period of 24 h post-emergence is generally required for the completion of sexual maturation, which in males includes a 180degrees rotation of the genital ...201121595988
secretion of anti-plasmodium effector proteins from a natural isolate pantoea agglomerans using pelb and hlya secretion signals.the insect-vectored disease malaria is a major world health problem. new control strategies are needed to supplement the current use of insecticides and medications. a genetic approach can be used to inhibit development of the malaria parasite (plasmodium sp.) in the mosquito host. we hypothesized that pantoea agglomerans, a bacterial symbiont of anopheles mosquitoes, could be engineered to express and secrete anti-plasmodium effector proteins, a strategy termed paratransgenesis. to this end, pl ...201121602368
the dominant anopheles vectors of human malaria in the asia-pacific region: occurrence data, distribution maps and bionomic precis.abstract: background: the final article in a series of three publications examining the global distribution of 41 dominant vector species (dvs) of malaria is presented here. the first publication examined the dvs from the americas, with the second covering those species present in africa, europe and the middle east. here we discuss the 19 dvs of the asian-pacific region. this region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence ...201121612587
transition of plasmodium sporozoites into liver stage-like forms is regulated by the rna binding protein pumilio.many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve rna binding proteins as regulators of translation of key mrnas. in malaria parasites (plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. ...201121625527
studies on larvicidal and pupicidal activity of leucas aspera willd. (lamiaceae) and bacterial insecticide, bacillus sphaericus, against malarial vector, anopheles stephensi liston. (diptera: culicidae).the efficacy of whole plant extracts of leucas aspera and bacillus sphaericus has been proven against larvicidal and pupicidal activities of the malarial vector, anopheles stephensi. the present study investigated the larvicidal and pupicidal activity against the first to fourth instar lavae and pupae of the laboratory-reared mosquitoes, a. stephensi. the medicinal plants were collected from the area around maruthamalai hills, coimbatore, tamil nadu, india. l. aspera whole plant was washed with ...201121626422
efficacy of plant-mediated synthesized silver nanoparticles against hematophagous parasites.the purpose of the present study was to investigate the acaricidal and larvicidal activity against the larvae of haemaphysalis bispinosa neumann (acarina: ixodidae) and larvae of hematophagous fly hippobosca maculata leach (diptera: hippoboscidae) and against the fourth-instar larvae of malaria vector, anopheles stephensi liston, japanese encephalitis vector, culex tritaeniorhynchus giles (diptera: culicidae) of synthesized silver nanoparticles (agnps) utilizing aqueous leaf extract from musa pa ...201121638210
early transcriptional responses of hepg2-a16 liver cells to infection by plasmodium falciparum sporozoites.invasion of hepatocytes by plasmodium sporozoites deposited by anopheles mosquitoes, and their subsequent transformation into infective merozoites is an obligatory step in the initiation of malaria. interactions between the sporozoites and hepatocytes lead to a distinct, complex and coordinated cellular and systemic host response. little is known about host liver cell response to sporozoite invasion, or whether it is primarily adaptive for the parasite, for the host, or for both. our present stu ...201121652718
a role for heparan sulfate proteoglycans in plasmodium falciparum sporozoite invasion of anopheline mosquito salivary glands.hs (heparan sulfate) has been shown to be an important mediator of plasmodium sporozoite homing and invasion of the liver, but the role of this glycosaminoglycan in mosquito vector host-sporozoite interactions is unknown. we have biochemically characterized the function of agoxt1 (anopheles gambiae peptide-o-xylosyltransferase 1) and confirmed that agoxt1 can modify peptides representing model hs and chondroitin sulfate proteoglycans in vitro. moreover, we also demonstrated that the mosquito sal ...201121663594
the puf-family rna-binding protein puf2 controls sporozoite conversion to liver stages in the malaria parasite.malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus plasmodium. during host switch the malaria parasite employs specialized latent stages that colonize the new host environment. previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. sexual parasite development is controlled by a ...201121673790
reduction in host-finding behaviour in fungus-infected mosquitoes is correlated with reduction in olfactory receptor neuron responsiveness.abstract: background: chemical insecticides against mosquitoes are a major component of malaria control worldwide. fungal entomopathogens formulated as biopesticides and applied as insecticide residual sprays could augment current control strategies and mitigate the evolution of resistance to chemical-based insecticides. methods: anopheles stephensi mosquitoes were exposed to beauveria bassiana or metarhizium acridum fungal spores and sub-lethal effects of exposure to fungal infection were studi ...201121812944
bacillus amyloliquefaciens: a mosquitocidal bacterium from mangrove forests of andaman & nicobar islands, india.samples collected from the mangrove forests of andaman & nicobar islands yielded a mosquitocidal bacterium, whose extracellular metabolite(s) exhibited mosquito larvicidal and pupicidal activity. the bacterium was isolated using standard microbiological methods and identified using classical biochemical tests and rpob gene sequences. the mosquitocidal bacterium was identified as bacillus amyloliquefaciens. mosquitocidal metabolite(s) was separated from the culture supernatant of the bacterium an ...201121810402
design and evaluation of primaquine-artemisinin hybrids as a multistage anti-malarial strategy.it is widely accepted that the struggle against malaria depends on the development of new strategies to fight infection. the "magic bullet" thought to be necessary to reach eradication should not only provide treatment for all plasmodium sp. that infect human red blood cells but also eliminate the replicative and dormant liver forms of the parasite. moreover, these goals should ideally be achieved by using different mechanisms of action to avoid the development of resistance. to that end, two hy ...201121807973
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