Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Death by apoptosis regulates cell numbers in metazoan tissues and it is mediated by activation of caspases and results in characteristic morphological and biochemical changes. We report here that the malaria protozoan, Plasmodium berghei, exhibits features typical of metazoan apoptotic cells including condensation of chromatin, fragmentation of the nuclear DNA and movement of phosphatidylserine from the inner to the outer lamellae of the cell membrane. In addition, proteins with caspase-like activity were identified in the cytoplasm of the ookinete suggesting that the cellular mechanism of cell death may be similar to that of multicellular eukaryotes. Our data show that more than 50% of the mosquito midgut stages of the parasite die naturally by apoptosis before gut invasion. Cell death was prevented by a caspase inhibitor, treatment resulting in a doubling of parasite intensity. All these features also occur in vitro. Cell suicide thus plays a major and hitherto unrecognised role in controlling parasite populations and could be a novel target for malaria control strategies.
 ...
PMID:Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. 1211 96

Malaria kills millions of people every year, and new control measures are urgently needed. The recent demonstration that (effector) genes can be introduced into the mosquito germ line to diminish their ability to transmit the malaria parasite offers new hope toward the fight of the disease (Ito, J., Ghosh, A., Moreira, L. A., Wimmer, E. A. & Jacobs-Lorena, M. (2002) Nature, 417, 452-455). Because of the high selection pressure that an effector gene imposes on the parasite population, development of resistant strains is likely to occur. In search of additional antiparasitic effector genes, we have generated transgenic Anopheles stephensi mosquitoes that express the bee venom phospholipase A2 (PLA2) gene from the gut-specific and blood-inducible Anopheles gambiae carboxypeptidase (AgCP) promoter. Northern blot analysis indicated that the PLA2 mRNA is specifically expressed in the guts of transgenic mosquitoes with peak expression at approximately 4 h after blood ingestion. Western blot and immunofluorescence analyses detected PLA2 protein in the midgut epithelia of transgenic mosquitoes from 8 to 24 h after a blood meal. Importantly, transgene expression reduced Plasmodium berghei oocyst formation by 87% on average and greatly impaired transmission of the parasite to naive mice. The results indicate that PLA2 may be used as an additional effector gene to block the development of the malaria parasite in mosquitoes.
 ...
PMID:Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes. 1216 27

Toll-like receptors (TLRs) are a group of evolutionary conserved proteins with diverse biological functions. In Drosophila melanogaster, Toll protein plays an important role in pattern formation in embryogenesis and in antimicrobial immunity in larvae and adults. In insects, Toll and two other related proteins, Tehao and 18-wheeler have been shown to participate in the activation of the innate immune responses to fungal and bacterial pathogens. In this paper we report the cloning and characterization of four TLR gene from malaria vector mosquito Anopheles gambiae, AgToll, AgToll6, AgTrex, and AgToll9, orthologues of DmToll, DmToll6, DmTollo (Toll8) and DmToll9 (CG5528) in Drosophila melanogaster. The expression profiles of these genes during development, in different adult tissues and after immune challenge were examined. As expected for the orthologue of Drosophila Toll, AgToll was found to be expressed highly in the ovary and may play a role in pattern formation during embryogenesis. AgToll9, surprisingly, was found to be highly expressed in the adult gut. The potential roles of these genes in development and immunity were discussed.
 ...
PMID:Characterization of four Toll related genes during development and immune responses in Anopheles gambiae. 1221 52

The genomic locus SRPN10 of the malaria vector Anopheles gambiae codes for four alternatively spliced serine protease inhibitors of the serpin superfamily. The four 40- to 42-kDa isoforms differ only at their C terminus, which bears the reactive site loop, and exhibit protein sequence similarity with other insect serpins and mammalian serpins of the ovalbumin family. Inhibition experiments with recombinant purified SRPN10 serpins reveal distinct and specific inhibitory activity of three isoforms toward different proteases. All isoforms are mainly expressed in the midgut but also in pericardial cells and hemocytes of the mosquito. The cellular localization of SRPN10 serpins is nucleocytoplasmic in pericardial cells, in hemocytes and in a hemocyte-like mosquito cell line, but in the gut the proteins are mostly localized in the nucleus. Although the transcript levels of all SRPN10 isoforms are marginally affected by bacterial challenge, the transcripts of two isoforms (KRAL and RCM) are induced in female mosquitoes in response to midgut invasion by Plasmodium berghei ookinetes. The KRAL and RCM SRPN10 isoforms represent new potential markers to study the ookinete midgut invasion process in anopheline mosquitoes.
 ...
PMID:Cloning and characterization of four Anopheles gambiae serpin isoforms, differentially induced in the midgut by Plasmodium berghei invasion. 1245 78

We examined the predator-prey relationship between larvae of the malaria mosquito Anopheles gambiae and nymphs of the dragonfly (Libellulidae). Studies were conducted to determine whether polymerase chain reaction (PCR) can be used to detect DNA of An. gambiae in the gut of libellulid nymphs, and to determine how long after feeding on An. gambiae that mosquito DNA remains detectable by PCR. Total DNA was extracted from the gut contents of libellulid nymphs by using 2 types of DNA extraction methods. The target sequence for the diagnostic PCR was the intergenic spacer regions of the ribosomal DNA gene locus. These sequences were analyzed by using An. gambiae complex-specific primers. After analyzing nymphal gut contents with PCR at regular postfeed intervals, a 390-base pair product could be amplified. The presence of mosquito larvae was visually confirmed for up to 40 min after feeding. Regardless of the number of mosquito larvae ingested, libellulid gut contents could be amplified or visually seen up to 1 h of digestion. This result indicates the nymphs have a high rate of digestion and that PCR with An. gambiae complex primers will be best utilized within 1 h after feeding as a detection system. This study confirmed that dragonfly nymphs feed well on anopheline larvae, and that mosquito DNA, although rapidly digested, can be successfully recovered and detected from within nymphal digestive tracts.
 ...
PMID:Determination of Anopheles gambiae larval DNA in the gut of insectivorous dragonfly (Libellulidae) nymphs by polymerase chain reaction. 1282 70

Plasmodium, the causative agent of malaria, has to undergo sexual differentiation and development in anopheline mosquitoes for transmission to occur. To isolate genes specifically induced in both organisms during the early stages of Plasmodium differentiation in the mosquito, two cDNA libraries were constructed, one enriched for sequences expressed in differentiating Plasmodium berghei ookinetes and another enriched for sequences expressed in Anopheles stephensi guts containing invading ookinetes and early oocysts. Sequencing of 457 ookinete library clones and 652 early oocyst clones represented 175 and 346 unique expressed sequence tags, respectively. Nine of 13 Plasmodium and four of the five Anopheles novel expressed sequence tags analyzed on Northern blots were induced during ookinete differentiation and mosquito gut invasion. Ancaspase-7, an Anopheles effector caspase, is proteolytically activated during Plasmodium invasion of the midgut. WARP, a gene encoding a Plasmodium surface protein with a von Willebrand factor A-like adhesive domain, is expressed only in ookinetes and early oocysts. An anti-WARP polyclonal antibody strongly inhibits (70-92%) Plasmodium development in the mosquito, making it a candidate antigen for transmission blocking vaccines. The present results and those of an accompanying report (Srinivasan, P., Abraham, E. G., Ghosh, A. K., Valenzuela, J., Ribeiro, J. M. C., Dimopoulos G., Kafatos, F. C., Adams, J. H., and Jacobs-Lorena, M. (2004) J. Biol. Chem. 279, 5581-5587) provide the foundation for further analysis of Plasmodium differentiation in the mosquito and of mosquito responses to the parasite.
 ...
PMID:Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. 1462 12

Malaria ranks among the deadliest infectious diseases that kills more than one million persons every year. The mosquito is an obligatory vector for malaria transmission. In the mosquito, Plasmodium undergoes a complex series of developmental events that includes transformation into several distinct morphological forms and the crossing of two different epithelia--midgut and salivary gland. Circumstantial evidence suggests that crossing of the epithelia requires specific interactions between Plasmodium and epithelial surface molecules. By use of a phage display library we have identified a small peptide-SM1--that binds to the surfaces of the mosquito midgut and salivary glands. Transgenic Anopheles stephensi mosquitoes expressing a SM1 tetramer from a blood-inducible and gut-specific promoter are substantially impaired in their ability to sustain parasite development and transmission. A second effector gene, phospholipase A2, also impairs parasite transmission in transgenic mosquitoes. These findings have important implications for the development of new strategies for malaria control.
 ...
PMID:Interrupting malaria transmission by genetic manipulation of anopheline mosquitoes. 1511 75

Transmission-blocking vaccines prevent the development of Plasmodium parasite within the mosquito vector, thereby thwarting the spread of malaria through a community. The gold standard for determining the efficacy of a transmission-blocking vaccine is the standard membrane feeding assay. This assay requires the dissection of mosquitoes and microscopic counting of oocysts present on the mosquito mid-gut, typically at 7-10 days p.i. Here we describe a real-time quantitative PCR assay that is rapid, target-specific and robust, with a sensitive detection threshold and which may be employed earlier p.i. than the standard membrane feeding assay and is applicable to preserved material. The real-time PCR assay utilises the LightCycler platform and SYBR Green I detection system to amplify 180 bp of the asexual form of the Plasmodium falciparum rRNA gene. It has a quantitative range of greater than four orders of magnitude and a detection threshold of 10 parasites. Validation experiments using a monoclonal antibody of known blocking activity revealed the real-time PCR assay to give equivalent results to the standard membrane feeding assay. In addition, the PCR assay can establish the effect of such a monoclonal antibody on the parasites' development within the oocyst and on the sporozoite (the transmissible stage) yield, providing a more pertinent assessment of transmission blocking activity than is possible by the standard membrane feeding assay. This assay may also be employed to monitor the sporogonic development of P. falciparum parasites within the mosquito vector.
 ...
PMID:A real-time PCR assay for quantifying Plasmodium falciparum infections in the mosquito vector. 1515 62

This review examines what is presently known of the molecular interactions between Plasmodium and Anopheles that take place in the latter's midgut upon ingestion of the parasites with an infectious blood meal. In order to become 'established' in the gut and to transform into a sporozoite-producing oocyst, the malaria parasite needs to undergo different developmental steps that are often characterized by the use of selected resources provided by the mosquito vector. Moreover, some of these resources may be used by the parasite in order to overcome the insect host's defence mechanisms. The molecular partners of this interplay are now in the process of being defined and analyzed for both Plasmodium and mosquito and, thus, understood; these will be presented here in some detail.
 ...
PMID:Interactions between malaria parasites and their mosquito hosts in the midgut. 1524 9

During the invasion of the mosquito midgut epithelium, Plasmodium ookinetes come to rest on the basal lamina, where they transform into the sporozoite-producing oocysts. Laminin, one of the basal lamina's major components, has previously been shown to bind several surface proteins of Plasmodium ookinetes. Here, using the recently developed RNAi technique in mosquitoes, we used a specific dsRNA construct targeted against the LANB2 gene (laminin gamma1) of Anopheles gambiae to reduce its mRNA levels, leading to a substantial reduction in the number of successfully developed oocysts in the mosquito midgut. Moreover, this molecular relationship is corroborated by the intimate association of developing P. berghei parasites and laminin in the gut, as observed using confocal microscopy. Our data support the notion of laminin playing a functional role in the development of the malaria parasite within the mosquito midgut.
 ...
PMID:Laminin and the malaria parasite's journey through the mosquito midgut. 1596 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>