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

Invasion of erythrocytes by malaria parasites involves multiple receptor-ligand interactions. To elucidate these pathways, we made use of four parasite clones with differing specificities for invasion, erythrocytes that are mutant for either glycophorin A or B, and enzyme modification of the erythrocyte surface with neuraminidase and trypsin. Neuraminidase alone abolishes invasion of two parasite clones (Dd2, FCR3/A2); these invade after trypsin treatment alone. A third clone (7G8) is unable to invade trypsin-treated erythrocytes. The fourth clone (HB3) can invade after either neuraminidase or trypsin treatment. The receptor for invasion of trypsin-treated erythrocytes was explored in two ways: treatment of trypsin-treated normal cells with neuraminidase, and trypsin treatment of glycophorin B-deficient cells. Both treatments eliminated invasion by all clones, indicating that the trypsin-independent pathway uses sialic acid and glycophorin B. To identify parasite proteins involved in the different pathways, erythrocyte binding assays were performed with soluble parasite proteins from each clone. Based on binding assays using erythrocytes that lack glycophorin A, the parasite protein known as EBA-175 appears to bind predominantly to glycophorin A. In contrast, the glycophorin B pathway does not appear to involve EBA-175, as binding of EBA-175 was similarly reduced to trypsin-treated normal and trypsin-treated glycophorin B-deficient erythrocytes. Thus, the glycophorin B-dependent, sialic acid-dependent invasion of trypsin-treated normal erythrocytes uses a different parasite ligand, indicating two or more sialic-dependent pathways for invasion. Clone 7G8, which cannot invade trypsin-treated erythrocytes, may be missing the ligand for invasion via glycophorin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycophorin B as an EBA-175 independent Plasmodium falciparum receptor of human erythrocytes. 807 23

Serine proteases are among the enzymes that play a crucial role during the digestion of the blood meal in the gut of mosquitoes. The identification of the corresponding genes would have important implications for the control of mosquitoes and mosquito-borne diseases. Analysis of the genomic organization of these genes may lead to the isolation of a gut-specific, inducible promoter for the expression of anti-parasitic agents in transgenic mosquitoes. Moreover, specific inhibitors could be designed on the basis of the structural properties of the enzymes. We report here on the identification of a trypsin gene family in Anopheles gambiae, the mosquito vector of malaria in Africa. Mosquito trypsin-related sequences were amplified by PCR using as template cDNA derived from RNA of blood fed mosquitoes. Cloning of the PCR product revealed two distinct sequences. Corresponding full-length cDNA clones were obtained and sequenced. Antryp1 and Antryp2 code for proteins of 274 and 277 amino acids respectively, showing 75% homology at the amino acid level. The deduced amino acid sequences clearly identify them as trypsins. Five additional trypsin sequences were found in overlapping genomic clones. The genes identified are tightly clustered within 11 kb and sequencing indicates that no introns are present. Northern and PCR analysis indicated that the transcription of both Antryp1 and Antryp2 is induced by blood feeding. Moreover, the Antryp1 protein was detected among the proteins of a midgut lysate of blood fed mosquitoes using antisera against recombinant Antryp1. In addition, the recombinant polypeptides derived from Antryp1 and Antryp2 expressed in Escherichia coli showed a strong proteolytic activity against different sets of blood proteins. We conclude that the products of Antryp1 and Antryp2 play an important role in the breakdown of the proteins during the digestion of the blood meal in the mosquito gut.
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PMID:Members of a trypsin gene family in Anopheles gambiae are induced in the gut by blood meal. 833 4

Control of malaria by a methodology that would permit the effective blockage of the Anopheles gambiae midgut wall penetration by Plasmodium parasites requires a detailed understanding of both the physiology of the mosquito's digestion, and of the interactions between the parasite and its host. We have transformed Drosophila melanogaster with several constructs that allow the study of the promoter region of two of the major late trypsin genes of A. gambiae. Using several deletions, we have identified, for both genes, small genomic segments that are sufficient to confer tissue specificity to the promoter in a species that is far away in evolution from the mosquito. This will allow further studies that will enable both the understanding of the blood meal digestion, and may potentially be useful for the design of anti-plasmodial constructs at a later stage.
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PMID:Conserved function of anopheles gambiae midgut-specific promoters in the fruitfly. 861 9

The peritrophic matrix (PM) that forms around a blood meal is a potential barrier of Plasmodium development in mosquitoes. Previously, we have shown that to traverse the PM, Plasmodium ookinetes secrete a prochitinase and that an inhibitor of chitinase blocks further parasite development. Here we report that it is the mosquito trypsin that activates the Plasmodium prochitinase. Trypsin was identified as the chitinase-activating enzyme by two criteria: (i) trypsin activity and activating activity comigrated on one-dimensional gels, and (ii) activating activity and penetration of the PM by Plasmodium parasites were both hindered by trypsin-specific inhibitors. Subsequently, we examined the effect of antitrypsin antibodies on the parasite life cycle. Antibodies prepared against a recombinant blackfly trypsin effectively and specifically inhibited mosquito trypsin activity. Moreover, when incorporated into an infective blood meal, the antitrypsin antibodies blocked infectivity of Aedes aegypti mosquitoes by Plasmodium gallinaceum. This block of infectivity could be reversed by exogenously provided chitinase, strongly suggesting that the antibodies act by inhibiting prochitinase activation and not on the parasite itself. This work led to the identification of a mosquito antigen, i.e., midgut trypsin, as a novel target for blocking malaria transmission.
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PMID:Antibody-mediated inhibition of Aedes aegypti midgut trypsins blocks sporogonic development of Plasmodium gallinaceum. 864 75

The association between cytoadherence of Plasmodium falciparum-infected erythrocytes and the severity of malaria has been evaluated. In this study, we investigate adherence to C32 melanoma cells, CD36, intracellular adhesion molecule-1 (ICAM-1), thrombospondin (TSP), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and chondroitin sulfate A (CSA) of 36 P. falciparum isolates from patients suffering from acute falciparum malaria. Adherence to purified adhesion molecules varied greatly among different parasite isolates. All isolates but one adhered to CD36, but none bound to E-selectin and VCAM-1 beyond control levels. Some P. falciparum isolates adhered to ICAM-1 and to CSA, a newly identified receptor for adherence. There was no correlation between in vitro binding to any one receptor and the patients' conditions. In addition, we investigated the characteristics of adherence to CSA and to C32 melanoma cells. Infected erythrocytes continued to adhere after trypsin digestion and soluble CSA inhibited adherence to C32 melanoma cells in a dose-dependent manner. The results imply a role for CSA in the natural infection of P. falciparum.
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PMID:Cytoadherence characteristics of Plasmodium falciparum isolates from Thailand: evidence for chondroitin sulfate a as a cytoadherence receptor. 870 26

Trypsin production in the malaria vector Anopheles tessellatus Theobald peaks between 12 and 21 h after a blood meal. The presence of leupeptin or soybean trypsin inhibitor in a blood meal delayed the onset of maximal trypsin activity. Trypsin inhibitors in an infective blood meal increased the infectivity of Plasmodium vivax Grassi and decreased infectivity of P. falciparum Welch to An tessellatus. The opposite effects of trypsin inhibitors on infectivity of the 2 malaria parasites were attributed to differences in the biology of the parasites within the midgut of the vector, particularly the time of ookinete formation and the requirement for activation of a chitinase.
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PMID:Different effects of modulation of mosquito (Diptera:Culicidae) trypsin activity on the infectivity of two human malaria (Hemosporidia:Plasmodidae) parasites. 884 Jun 84

While studying the fate of heme generated during malaria infection, it was observed that mitochondrial preparations were highly enriched with heme compared to other subcellular particles. With this background, the present study aimed to determine the status of mitochondrial heme oxygenase and compare it with the microsomal enzyme. Mitochondrial and microsomal preparations were obtained from liver, spleen, kidney and brain of normal, inducer (cobalt chloride and hemin)-treated and Plasmodium berghei-infected Mastomys coucha. Heme oxygenase activity was determined by monitoring the formation of bilirubin. Biliverdin reductase activity was assayed by following the decrease in biliverdin content. Heme levels were measured by pyridine haemochromogen formation. Mitochondria from different tissues showed significant activity of heme oxygenase only after inducer (CoCl2 and hemin) treatment. In contrast, cerebral mitochondria did not show any enzyme activity. Hepatic, splenic and renal mitochondria of P. berghei-infected M. coucha showed noticeable heme oxygenase and biliverdin reductase activity. The response of hepatic mitochondrial heme oxygenase towards Triton X-100, trypsin, hydrogen peroxide, temperature, freezing and thawing and hemin was distinguishable from microsomal heme oxygenase. It is concluded that the mitochondria of different tissues from Mastomys display stress (biological and chemical)-induced activity of heme oxygenase. In addition, distinct differences between microsomal and mitochondrial heme oxygenase were observed.
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PMID:Mitochondrial heme oxygenase of Mastomys coucha. 893 Jan 30

Present understanding of the development of sexual stages of the human malaria parasites Plasmodium vivax and P.falciparum in the Anopheles vector is reviewed, with particular reference to the role of the mosquito midgut in establishing an infection. The sexual stages of the parasite, the gametocytes, are formed in human erythrocytes. The changes in temperature and pH encountered by the gametocyte induce gametogenesis in the lumen of the midgut. Macromolecules derived from mosquito tissue and second messenger pathways regulate events leading to fertilization. In An.tessellatus the movement of the ookinete from the lumen to the midgut epithelium is linked to the release of trypsin in the midgut and the peritrophic matrix is not a firm barrier to this movement. The passage of the P.vivax ookinete through the peritrophic matrix may take place before the latter is fully formed. The late ookinete development in P.falciparum requires chitinase to facilitate penetration of the peritrophic matrix. Recognition sites for the ookinetes are present on the midgut epithelial cells. N-acetyl glucosamine residues in the oligosaccharide side chains of An.tessellatus midgut glycoproteins and peritrophic matrix proteoglycan may function as recognition sites for P.vivax and P.falciparum ookinetes. It is possible that ookinetes penetrating epithelial cells produce stress in the vector. Mosquito molecules may be involved in oocyst development in the basal lamina, and encapsulation of the parasite occurs in vectors that are refractory to the parasite. Detailed knowledge of vector-parasite interactions, particularly in the midgut and the identification of critical mosquito molecules offers prospects for manipulating the vector for the control of malaria.
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PMID:Interactions of human malaria parasites, Plasmodium vivax and P.falciparum, with the midgut of Anopheles mosquitoes. 933 Feb 62

Chitinases that function in the molting of the larval exoskeleton have been characterized previously. However, chitinase expression in an adult insect gut has not been described. Here we report on the initial characterization and cloning of a novel chitinase gene that is expressed specifically in the midgut of adult Anopheles gambiae females. Upon feeding, chitinase is secreted into the gut lumen as an inactive pro-enzyme that is later activated by trypsin. Thus, temporal regulation of chitinase activity is tightly coupled to the temporal pattern of trypsin secretion. The enzyme may play a role in structuring the chitin-containing extracellular peritrophic matrix, whose formation is also induced by feeding. A chitinase cDNA was cloned from a library enriched for gut-specific sequences. The open reading frame encodes a 525-amino acid protein comprised of a putative catalytic domain at the N terminus, a putative chitin-binding domain at the C terminus, and a threonine/serine/proline-rich amino acid stretch in between them. Northern analysis indicates that this chitinase is expressed exclusively in the guts of adult females and not in adult carcasses or in any larval or pupal tissues. The present findings suggest the possibility of using this chitinase as an antigen for a malaria transmission-blocking vaccine.
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PMID:Characterization of a novel gut-specific chitinase gene from the human malaria vector Anopheles gambiae. 936 Sep 58

A search for genes induced rapidly (< 3 h) after a blood meal in the gut of the human malaria vector Anopheles gambiae led to the identification of a carboxypeptidase gene (AgCP). We report the sequence of the 1302 nt AgCP transcribed sequence, 710 nt of upstream and 585 nt of downstream DNA. The AgCP open reading frame is 60.4% identical at the nucleotide level to a blackfly, Simulium vittatum, carboxypeptidase gene. The transcriptional start site of AgCP was determined by primer extension. Expression of AgCP mRNA is detectable in the guts of pupae and sugar-fed adult female mosquitoes and is induced (approximately 10-fold) within 3 h of a blood meal. By 24 h after a blood meal, mRNA abundance returns to a level close to that present before a blood meal. Whole-mount in situ hybridization shows that AgCP mRNA expression is restricted to most or all cells of the posterior midgut. Expression of the AgCP and trypsin genes were compared and shown to differ in two fundamental ways: (1) the peak of AgCP expression after a blood meal occurs approximately 20 h before that of trypsin; and (2) induction of the AgCP gene is independent of the composition of the ingested meal whereas trypsin induction requires the presence of protein. The potential use of the AgCP promoter for driving the expression of genes that hinder the development of parasites in the mosquito gut is discussed.
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PMID:Rapid induction by a blood meal of a carboxypeptidase gene in the gut of the mosquito Anopheles gambiae. 956 47


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