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

Mice were orally and nasally immunised with a malaria parasite protein, MSA2, expressed in Lactococcus lactis, covalently attached to the peptidoglycan (MSA2cP), or non-covalently rebound to L. lactis cell walls, live Lactobacillus reuteri and Lb. salivarius (MSA2cA). Although there was marked variation within mice of the same inbred strain, the data suggest that the characteristics of serum IgG antibodies formed against MSA2 are influenced by the mouse strain and mode of MSA2 presentation. MSA2-specific IgA antibodies in sera and faecal pellets, and IFNgamma-secreting spleen cells were detectable in some immunised animals. MSA2cA on lactobacilli, although not effective in eliciting serum IgG antibodies, showed a potential for eliciting IgA antibodies in the gut. The presence of MSA2 in L. lactis tended to divert the antibody response from lactococcal antigens. The data suggest that anti-MSA2 and anti-lactococcal antibody responses are not necessarily associated in the mice. The findings are related to the use of lactic acid bacteria expressing heterologous proteins for therapy and vaccination.
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PMID:Mucosal immunisation of mice with malaria protein on lactic acid bacterial cell walls. 1728 Jul 49

Here, we show that an alpha-proteobacterium of the genus Asaia is stably associated with larvae and adults of Anopheles stephensi, an important mosquito vector of Plasmodium vivax, a main malaria agent in Asia. Asaia bacteria dominate mosquito-associated microbiota, as shown by 16S rRNA gene abundance, quantitative PCR, transmission electron microscopy and in situ-hybridization of 16S rRNA genes. In adult mosquitoes, Asaia sp. is present in high population density in the female gut and in the male reproductive tract. Asaia sp. from An. stephensi has been cultured in cell-free media and then transformed with foreign DNA. A green fluorescent protein-tagged Asaia sp. strain effectively lodged in the female gut and salivary glands, sites that are crucial for Plasmodium sp. development and transmission. The larval gut and the male reproductive system were also colonized by the transformed Asaia sp. strain. As an efficient inducible colonizer of mosquitoes that transmit Plasmodium sp., Asaia sp. may be a candidate for malaria control.
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PMID:Bacteria of the genus Asaia stably associate with Anopheles stephensi, an Asian malarial mosquito vector. 1750 6

A century after Sir Ronal Ross' discovery of the malaria parasite in the mosquito gut, unveiling the mode of malaria transmission, 40 per cent of the global population is still exposed to the disease. The exposed population lives in the tropical world. Africa bears the heaviest burden of the disease estimated at 31.6 million DALYs equivalent to 62.1 DALYs per 1,000 population. Children and pregnant women are the most affected groups. Control methods of source reduction which were effective in Europe and America using DDT spraying, larviciding and drainage of swamps and stagnant waters were not effective in the tropics. The complexity of the disease, the parasite' life cycle and the tropical environment within which it thrives calls for a new approach to malaria control, multilateral collaboration and funding an d above all commitment from the south and south-south collaboration. The long-term challenge lies on the discovery of better methods for malaria control. However, Africa cannot wait. Better utilization of existing tools exploiting their synergistic effect will save millions of lives.
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PMID:The future of malaria research and control: An African perspective. 1758 Oct 6

Toxicities of three chitin synthesis inhibitors (diflubenzuron, nikkomycin Z and polyoxin D) were evaluated using second instars of the common malaria mosquito, Anopheles quadrimaculatus Say (Diptera: Culicidae). Neither nikkomycin Z nor polyoxin D at 50 microg/liter caused significant larval mortality, although they reduced the body weight of the survivors by 20.5 and 33.8%, respectively, in 48 h. In contrast, exposures of the larvae to diflubenzuron at 12.5 microg/liter for 48 h resulted in 86.7% larval mortality and reduced the body weight of the survivors by 29.1%. Exposure of the pupae (<12 h old) to diflubenzuron at 100 microg/liter for 48 h caused 18.9% pupal mortality and consequently reduced the adult emergence by 24.7% from the surviving pupae. Furthermore, exposure of third instars to diflubenzuron at 4, 20, 100, and 500 microg/liter for 24 h resulted in the reduction of larval chitin contents by 4.25, 33.2, 35.2, and 57.7%, respectively. Such an effect seemed to be associated with only cuticular chitin synthesis because the same exposures did not significantly affect chitin contents in the guts. Our results indicated that diflubenzuron was highly toxic to second instars by not only causing high larval mortality but also by affecting their growth. Diflubenzuron was also fairly toxic to pupae by not only causing pupal mortality but also affecting the adult emergence. Our results suggest that diflubenzuron might affect only chitin synthesis in the cuticle but not in the peritrophic matrix, which is probably due to diflubenzuron's direct contact to mosquito larvae in water, slow distribution in insect body, rapid degradation in the insect gut, or a combination.
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PMID:Comparative studies on effects of three chitin synthesis inhibitors on common malaria mosquito (Diptera: Culicidae). 1804 5

A bioinformatics-based investigation of three insect species with completed genome sequences has revealed that insect chitinase-like proteins (glycosylhydrolase family 18) are encoded by a rather large and diverse group of genes. We identified 16, 16 and 13 putative chitinase-like genes in the genomic databases of the red flour beetle, Tribolium castaneum, the fruit fly, Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae, respectively. Chitinase-like proteins encoded by this gene family were classified into five groups based on phylogenetic analyses. Group I chitinases are secreted proteins that are the most abundant such enzymes in molting fluid and/or integument, and represent the prototype enzyme of the family, with a single copy each of the catalytic domain and chitin-binding domain (ChBD) connected by an S/T-rich linker polypeptide. Group II chitinases are unusually larger-sized secreted proteins that contain multiple catalytic domains and ChBDs. Group III chitinases contain two catalytic domains and are predicted to be membrane-anchored proteins. Group IV chitinases are the most divergent. They usually lack a ChBD and/or an S/T-rich linker domain, and are known or predicted to be secreted proteins found in gut or fat body. Group V proteins include the putative chitinase-like imaginal disc growth factors (IDGFs). In each of the three insect genomes, multiple genes encode group IV and group V chitinase-like proteins. In contrast, groups I-III are each represented by only a singe gene in each species.
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PMID:Domain organization and phylogenetic analysis of the chitinase-like family of proteins in three species of insects. 1834 50

The nutrient amino acid transporter (NAT) subfamily is the largest subdivision of the sodium neurotransmitter symporter family (SNF; also known as SLC6; HUGO). There are seven members of the NAT population in the African malaria mosquito Anopheles gambiae, two of which, AgNAT6 and AgNAT8, preferably transport indole- and phenyl-branched substrates, respectively. The relative expression and distribution of these aromatic NATs were examined with transporter-specific antibodies in Xenopus oocytes and mosquito larval alimentary canal, representing heterologous and tissue expression systems, respectively. NAT-specific aromatic-substrate-induced currents strongly corresponded with specific accumulation of both transporters in the plasma membrane of oocytes. Immunolabeling revealed elevated expressions of both transporters in specific regions of the larval alimentary canal, including salivary glands, cardia, gastric caeca, posterior midgut and Malpighian tubules. Differences in relative expression densities and spatial distribution of the transporters were prominent in virtually all of these regions, suggesting unique profiles of the aromatic amino acid absorption. For the first time reversal of the location of a transporter between apical and basal membranes was identified in posterior and anterior epithelial domains corresponding with secretory and absorptive epithelial functions, respectively. Both aromatic NATs formed putative homodimers in the larval gut whereas functional monomers were over-expressed heterologously in Xenopus oocytes. The results unequivocally suggest functional synergy between substrate-specific AgNAT6 and AgNAT8 in intracellular absorption of aromatic amino acids. More broadly, they suggest that the specific selectivity, regional expression and polarized membrane docking of NATs represent key adaptive traits shaping functional patterns of essential amino acid absorption in the metazoan alimentary canal and other tissues.
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PMID:Synergy and specificity of two Na+-aromatic amino acid symporters in the model alimentary canal of mosquito larvae. 1845 87

Symbiotic bacteria have been proposed as tools for control of insect-borne diseases. Primary requirements for such symbionts are dominance, prevalence and stability within the insect body. Most of the bacterial symbionts described to date in Anopheles mosquitoes, the vector of malaria in humans, have lacked these features. We describe an alpha-Proteobacterium of the genus Asaia, which stably associates with several Anopheles species and dominates within the body of An. stephensi. Asaia exhibits all the required ecological characteristics making it the best candidate, available to date, for the development ofa paratransgenic approach for manipulation of mosquito vector competence. Key features of Asaia are: (i) dominance within the mosquito-associated microflora, as shown by clone prevalence in 16S rRNA gene libraries and quantitative real time Polymerase Chain Reaction (qRT-PCR); (ii) cultivability in cell-free media; (iii) ease of transformation with foreign DNA and iv) wide distribution in the larvae and adult mosquito body, as revealed by transmission electron microscopy, and in situ-hybridization experiments. Using a green fluorescent protein (GFP)-tagged Asaia strain, it has been possible to show that it effectively colonizes all mosquito body organs necessary for malaria parasite development and transmission, including female gut and salivary glands. Asaia was also found to massively colonize the larval gut and the male reproductive system of adult mosquitoes. Moreover, mating experiments showed an additional key feature necessary for symbiotic control, the high transmission potential of the symbiont to progeny by multiple mechanisms. Asaia is capable of horizontal infection through an oral route during feeding both in preadult and adult stages and through a venereal pattern during mating in adults. Furthermore, Asaia is vertically transmitted from mother to progeny indicating that it could quickly spread in natural mosquito populations.
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PMID:Bacteria of the genus Asaia: a potential paratransgenic weapon against malaria. 1851 13

We present a metabolism-driven top-down systems biology approach to characterize metabolic changes in the mouse resulting from an infection with Plasmodium berghei, using high-resolution (1)H NMR spectroscopy and multivariate data analysis techniques. Twelve female NMRI mice were infected intravenously with approximately 20 million P. berghei-parasitized erythrocytes. Urine and plasma samples were collected 4-6 h before infection, and at days 1, 2, 3, and 4 postinfection. Multivariate analysis of spectral data showed differentiation between samples collected before and after infection, with growing metabolic distinction as the time postinfection progressed. Our analysis of plasma from P. berghei-infected mice showed marked increases in lactate and pyruvate levels, and decreased glucose, creatine, and glycerophosphoryl choline compared with preinfection, indicating glycolytic upregulation, and increased energy demand due to P. berghei infection. The dominant changes in the urinary metabolite profiles included increased levels of pipecolic acid, phenylacetylglycine, and dimethylamine, and decreased concentrations of taurine and trimethylamine- N-oxide, which may, among other factors, indicate a disturbance of the gut microbial community caused by the parasite. Although several of the observed metabolic changes are also associated with other parasitic infections, the combination of metabolic changes and, in particular, the occurrence of pipecolic acid in mouse urine postinfection are unique to a P. berghei infection. Hence, metabolic profiling may provide a sensitive diagnostic tool of Plasmodium infection and the control of malaria more generally.
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PMID:Global metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. 1864 85

In a paratransgenic approach, genetically modified bacteria are utilized to kill the parasite in the vector gut. A critical component for paratransgenics against malaria is how transgenic bacteria can be introduced and then kept in a mosquito population. Here, we investigated transstadial and horizontal transfer of bacteria within an Anopheles gambiae mosquito colony with the focus on spiked breeding sites as a possible means of introducing bacteria to mosquitoes. A Pantoea stewartii strain, previously isolated from An. gambiae, marked with a green fluorescent protein (GFP), was introduced to mosquitoes in different life stages. The following life stages or older mosquitoes in the case of adults were screened for bacteria in their guts. In addition to P. stewartii other bacteria were isolated from the guts: these were identified by 16S rRNA sequence analysis and temporal temperature gradient gel electrophoresis (TTGE). Bacteria were transferred from larvae to pupae but not from pupae to adults. The mosquitoes were able to take up bacteria from the water they emerged from and transfer the same bacteria to the water they laid eggs in. Elizabethkingia meningoseptica was more often isolated from adult mosquitoes than P. stewartii. A bioassay was used to examine An. gambiae oviposition responses towards bacteria-containing solutions. The volatiles emitted from the solutions were sampled by headspace-solid phase microextraction (SPME) and identified by gas chromatography and mass spectrometry (GC-MS) analysis. P. stewartii but not E. meningoseptica mediated a positive oviposition response. The volatiles emitted by P. stewartii include indole and 3-methyl-1-butanol, which previously have been shown to affect An. gambiae mosquito behaviour. E. meningoseptica emitted indole but not 3-methyl-1-butanol, when suspended in saline. Taken together, this indicates that it may be possible to create attractive breeding sites for distribution of genetically modified bacteria in the field in a paratransgenic approach against malaria. Further research is needed to determine if the bacteria are also transferred in the same way in nature.
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PMID:Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (Diptera: Culicidae) and oviposition response to bacteria-containing water. 1867 31

Molecules and cellular mechanisms that regulate the process of cell division in malaria parasites remain poorly understood. In this study we isolate and characterize the four Plasmodium falciparum centrins (PfCENs) and, by growth complementation studies, provide evidence for their involvement in cell division. Centrins are cytoskeleton proteins with key roles in cell division, including centrosome duplication, and possess four Ca(2+)-binding EF hand domains. By means of phylogenetic analysis, we were able to decipher the evolutionary history of centrins in eukaryotes with particular emphasis on the situation in apicomplexans and other alveolates. Plasmodium possesses orthologs of four distinct centrin paralogs traceable to the ancestral alveolate, including two that are unique to alveolates. By real time PCR and/or immunofluorescence, we determined the expression of PfCEN mRNA or protein in sporozoites, asexual blood forms, gametocytes, and in the oocysts developing inside mosquito mid-gut. Immunoelectron microscopy studies showed that centrin is expressed in close proximity with the nucleus of sporozoites and asexual schizonts. Furthermore, confocal and widefield microscopy using the double staining with alpha-tubulin and centrin antibodies strongly suggested that centrin is associated with the parasite centrosome. Following the episomal expression of the four PfCENs in a centrin knock-out Leishmania donovani parasite line that exhibited a severe growth defect, one of the PfCENs was able to partially restore Leishmania growth rate and overcome the defect in cytokinesis in such mutant cell line. To our knowledge, this study is the first characterization of a Plasmodium molecule that is involved in the process of cell division. These results provide the opportunity to further explore the role of centrins in cell division in malaria parasites and suggest novel targets to construct genetically modified, live attenuated malaria vaccines.
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PMID:Centrins, cell cycle regulation proteins in human malaria parasite Plasmodium falciparum. 1869 42


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