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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular studies of insect disease vectors are of paramount importance for understanding parasite-vector relationship. Advances in this area have led to important findings regarding changes in vectors' physiology upon blood feeding and parasite infection. Mechanisms for interfering with the vectorial capacity of insects responsible for the transmission of diseases such as malaria, Chagas disease and dengue fever are being devised with the ultimate goal of developing transgenic insects. A primary necessity for this goal is information on gene expression and control in the target insect. Our group is investigating molecular aspects of the interaction between Leishmania parasites and Lutzomyia sand flies. As an initial step in our studies we have used random sequencing of cDNA clones from two expression libraries made from head/thorax and abdomen of sugar fed L. longipalpis for the identification of expressed sequence tags (EST). We applied differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR to characterize differentially expressed mRNA from sugar and blood fed insects, and, in one case, from a L. (V.) braziliensis-infected L. longipalpis. We identified 37 cDNAs that have shown homology to known sequences from GeneBank. Of these, 32 cDNAs code for constitutive proteins such as zinc finger protein, glutamine synthetase, G binding protein, ubiquitin conjugating enzyme. Three are putative differentially expressed cDNAs from blood fed and Leishmania-infected midgut, a chitinase, a V-ATPase and a MAP kinase. Finally, two sequences are homologous to Drosophila melanogaster gene products recently discovered through the Drosophila genome initiative.
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PMID:Characterization of constitutive and putative differentially expressed mRNAs by means of expressed sequence tags, differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR from the sand fly vector Lutzomyia longipalpis. 1128 81

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < or = 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.
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PMID:Exploring the transcriptome of the malaria sporozoite stage. 1149 95

A novel mosquito antimicrobial peptide, gambicin, and the corresponding gene were isolated in parallel through differential display-PCR, an expressed sequence tag (EST) project, and characterization of an antimicrobial activity in a mosquito cell line by reverse-phase chromatography. The 616-bp gambicin ORF encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide bridges. Gambicin lacks sequence homology with other known proteins. Like other Anopheles gambiae antimicrobial peptide genes, gambicin is induced by natural or experimental infection in the midgut, fatbody, and hemocyte-like cell lines. Within the midgut, gambicin is predominantly expressed in the anterior part. Both local and systemic gambicin expression is induced during early and late stages of natural malaria infection. In vitro experiments showed that the 6.8-kDa mature peptide can kill both Gram-positive and Gram-negative bacteria, has a morphogenic effect on a filamentous fungus, and is marginally lethal to Plasmodium berghei ookinetes. An oxidized form of gambicin isolated from the cell line medium was more active against bacteria than the nonoxidized form from the same medium.
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PMID:Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. 1160 51

An important justification for genome sequencing efforts is the anticipation that data from model organisms will provide a framework for the more rapid analysis of other, less studied genomes. In this investigation, we sequenced an internal region of 25 amino acids from a 52 kDa protein that was differentially expressed in 20-hydroxyecdysone-treated Aedes albopictus cells in culture. Within the GenBank non-mouse and non-human expressed sequence tag (EST) database, this "Aedes peptide" uncovered a putative homology to hypothetical translation products from Anopheles gambiae, Caenorhabditis elegans and Drosophila melanogaster. The hypothetical translation product from D. melanogaster, which included 462 amino acids, uncovered five expressed sequence tags (ESTs) from the malaria vector, Anopheles gambiae. When the Anopheles ESTs were aligned against the hypothetical Drosophila protein, we found that in aggregate they covered 324 amino acids, with gaps measuring 19, 30, and 87 amino acids. To approximate the complete amino acid sequence, gaps between translation products from Anopheles ESTs were replaced with corresponding amino acids from Drosophila to arrive at a calculated mass of 51 104 and a pI of 5.84 for the mosquito protein, consistent with the position of the Ae. albopictus protein on two-dimensional polyacrylamide gels. Finally, tandem mass spectrometry of a tryptic digest of the 52 kDa Ae. albopictus protein revealed 33 peptides with masses within 1 Dalton of those predicted from an in silico digestion of the reconstructed Anophleles protein. In addition to providing the first direct evidence that a hypothetical protein in Drosophila is in fact translated, this analysis provides a general approach for maximizing recovery, from existing databases, of information that can facilitate prioritization of efforts among several candidate proteins.
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PMID:Leveraging genomic databases: from an Aedes albopictus mosquito cell line to the malaria vector Anopheles gambiae via the Drosophila genome project. 1196 84

Mosquito-borne diseases, including dengue, malaria, and lymphatic filariasis, exact a devastating toll on global health and economics, killing or debilitating millions every year (54). Mosquito innate immune responses are at the forefront of concerted research efforts aimed at defining potential target genes that could be manipulated to engineer pathogen resistance in vector populations. We aimed to describe the pivotal role that circulating blood cells (called hemocytes) play in immunity by generating a total of 11,952 Aedes aegypti and 12,790 Armigeres subalbatus expressed sequence tag (EST) sequences from immune response-activated hemocyte libraries. These ESTs collapsed into 2,686 and 2,107 EST clusters, respectively. The clusters were used to adapt the web-based interface for annotating bacterial genomes called A Systematic Annotation Package for Community Analysis of Genomes (ASAP) for analysis of ESTs. Each cluster was categorically characterized and annotated in ASAP based on sequence similarity to five sequence databases. The sequence data and annotations can be viewed in ASAP at https://asap.ahabs.wisc.edu/annotation/php/ASAP1.htm. The data presented here represent the results of the first high-throughput in vivo analysis of the transcriptome of immunocytes from an invertebrate. Among the sequences are those for numerous immunity-related genes, many of which parallel those employed in vertebrate innate immunity, that have never been described for these mosquitoes. The sequences and annotations presented in this paper have been submitted to GenBank under accession numbers AY 431103 to AY 433788 (Aedes aegypti) and AY 439334 to AY 441440 (Armigeres subalbatus).
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PMID:Description of the transcriptomes of immune response-activated hemocytes from the mosquito vectors Aedes aegypti and Armigeres subalbatus. 1521 57

Plastids are the organelles of plants and algae that house photosynthesis and many other biochemical pathways. Plastids contain a small genome, but most of their proteins are encoded in the nucleus and posttranslationally targeted to the organelle. When plants and algae lose photosynthesis, they virtually always retain a highly reduced "cryptic" plastid. Cryptic plastids are known to exist in many organisms, although their metabolic functions are seldom understood. The best-studied example of a cryptic plastid is from the intracellular malaria parasite, Plasmodium, which has retained a plastid for the biosynthesis of fatty acids, isoprenoids, and heme by the use of plastid-targeted enzymes. To study a completely independent transformation of a photosynthetic plastid to a cryptic plastid in another alga-turned-parasite, we conducted an expressed sequence tag (EST) survey of Helicosporidium. This parasite has recently been recognized as a highly derived green alga. Based on phylogenetic relationships to other plastid homologues and the presence of N-terminal transit peptides, we have identified 20 putatively plastid-targeted enzymes that are involved in a wide variety of metabolic pathways. Overall, the metabolic diversity of the Helicosporidium cryptic plastid exceeds that of the Plasmodium plastid, as it includes representatives of most of the pathways known to operate in the Plasmodium plastid as well as many others. In particular, several amino acid biosynthetic pathways have been retained, including the leucine biosynthesis pathway, which was only recently recognized in plant plastids. These two parasites represent different evolutionary trajectories in plastid metabolic adaptation.
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PMID:Nucleus-encoded genes for plastid-targeted proteins in Helicosporidium: functional diversity of a cryptic plastid in a parasitic alga. 1547 Feb 48

The identification and cloning of genes conferring mosquito refractoriness to the malaria parasite is critical for understanding malaria transmission mechanisms and holds great promise for developing novel approaches to malaria control. The mosquito midgut is the first major site of interaction between the parasite and the mosquito. Failure of the parasite to negotiate this environment can be a barrier for development and is likely the main cause of mosquito refractoriness. This paper reports a study on Aedes aegypti midgut expressed sequence tag (EST) identification and the determination of genes differentially expressed in mosquito populations susceptible and refractory to the avian malaria parasite Plasmodium gallinaceum. We sequenced a total of 1200 cDNA clones and obtained 1183 high-quality mosquito midgut ESTs that were computationally collapsed into 105 contigs and 251 singlets. All 1200 midgut cDNA clones, together with an additional 102 genetically or physically mapped Ae. aegypti clones, were spotted on single arrays with 12 replicates. Of those interrogated microarray elements, 28 (2.3%) were differentially expressed between the susceptible and refractory mosquito populations. Twenty-seven elements showed at least a two-fold increase in expression in the susceptible population level relative to the refractory population and one clone showed reduced expression. Sequence analysis of these differentially expressed genes revealed that 10 showed no significant similarity to any known genes, 6 clones had matches with unannotated genes of Anopheles gambiae, and 12 clones exhibited significant similarity to known genes. Real-time quantitative RT-PCR of selected clones confirmed the mRNA expression profiles from the microarray analysis.
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PMID:Microarray analysis for identification of Plasmodium-refractoriness candidate genes in mosquitoes. 1564 64

A microarray analysis of 14 900 genes of the malaria vector mosquito, Anopheles gambiae, shows that as many as 33% (4924) of their corresponding transcription products vary in abundance within 24 h after a blood meal. Approximately half (2388) of these products increase in their accumulation and the remainder (2536) decrease. Expression dynamics of 80% of the genes analysed by expressed sequence tag (EST) projects reported previously are consistent with the observations from this microarray analysis. Furthermore, the microarray analysis is more sensitive in detecting variation in abundance of gene products expressed at low levels and is more sensitive overall in that a greater number of regulated genes are detected. Major changes in transcript abundance were seen in genes encoding proteins involved in digestion, oogenesis and locomotion. The microarray data and an electronic hyperlinked version of all tables are available to the research community at http://www.angagepuci.bio.uci.edu/1/.
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PMID:Microarray analysis of genes showing variable expression following a blood meal in Anopheles gambiae. 1603 30

Artemisinin, a sesquiterpene lactone endoperoxide derived from the glandular secretory trichomes (GSTs) of Artemisia annua, provides the basis for the most effective treatments of malaria. The biology and biochemistry of GSTs of the Asteraceae and their biosynthesis of isoprenoids is reviewed. Recent efforts to understand the biosynthesis of artemisinin in A. annua GSTs are discussed in detail. This includes the development in the authors' laboratory of an expressed sequence tag (EST) approach to identifying the relevant biosynthetic genes using isolated GST as a source of mRNA. This has lead to the isolation of a cDNA encoding CYP71AV1, a multifunctional cytochrome P450 which catalyzes multiple oxidations of the sesquiterpene intermediate amorpha-4,11-diene to artemisinic acid. Further biochemical and molecular genetic work is required to elucidate the precise route from artemisinic alcohol to artemisinin and to engineer more efficient low cost production of artemisinin-based antimalarial drugs.
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PMID:Functional genomics and the biosynthesis of artemisinin. 1739 51

Rodent malaria parasites, such as Plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. Exploiting the available genetic sequence information, we constructed a cDNA library from the erythrocytic stages of P. berghei and analyzed the expressed sequence tag (EST). A total of 10,040 ESTs were generated and assembled into 2,462 clusters. These EST clusters were compared against public protein databases and 48 putative new transcripts, most of which were hypothetical proteins with unknown function, were identified. Genes encoding ribosomal or membrane proteins and purine nucleotide phosphorylases were highly abundant clusters in P. berghei. Protein domain analyses and the Gene Ontology functional categorization revealed translation/protein folding, metabolism, protein degradation, and multiple family of variant antigens to be mainly prevalent. The presently-collected ESTs and its bioinformatic analysis will be useful resources to identify for drug target and vaccine candidates and validate gene predictions of P. berghei.
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PMID:Expressed sequence tag analysis of the erythrocytic stage of Plasmodium berghei. 2207 21


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