共查询到20条相似文献,搜索用时 0 毫秒
1.
Malaria caused by the protozoan parasite Plasmodium falciparum is characterized by long-term, persistent infections that can last for many months. The ability of this parasite to avoid
clearance by the human immune system is dependent on its capacity to continuously alter the surface exposed antigenic proteins
that that are vulnerable to antibody recognition and attack, a process called antigenic variation. Significant work in recent
years has contributed to our understanding of the mechanisms underlying this process, including the genes encoding the antigenic
proteins and the DNA sequence elements that control their expression. In addition, the epigenetic “marks” that are associated
with activation and silencing of individual genes have been extensively characterized. These studies have led to a model that
includes multiple layers of regulation that ultimately lead to the tight coordination of expression of the genes responsible
for antigenic variation by malaria parasites. Here we review some more recent data that adds additional complexity to our
understanding of these regulatory layers. 相似文献
2.
Atefeh Taherian Fard Amna Salman Bahram Kazemi Habib Bokhari 《Parasitology research》2009,104(6):1361-1364
Malarial parasite has long been a subject of research for a large community of scientists and has yet to be conquered. One
of the main obstacles to effectively control this disease is rapidly evolving genetic structure of Plasmodium parasite itself. In this study, we focused on chromosome 4 of the Plasmodium falciparum and Plasmodium vivax species and carried out comparative studies of genes that are responsible for antigenic variation in respective species.
Comparative analysis of genes responsible for antigenic variation (var and vir genes in P. falciparum and P. vivax, respectively) showed significant difference in their respective nucleotide sequence lengths as well as amino acid composition.
The possible association of exon’s length on pathogenecity of respective Plasmodium species was also investigated, and analysis of gene structure showed that on the whole, exon lengths in P. falciparum are larger compared to P. vivax. Analysis of tandem repeats across the genome has shown that the size of repetitive sequences has a direct effect on chromosomes
length, which can also be a potential reason for P. falciparum’s greater variability and hence pathogenecity than P. vivax. 相似文献
3.
Sundaram Ravikumar Ganesan Ramanathan Samuel Jacob Inbaneson Andy Ramu 《Parasitology research》2011,108(1):107-113
The ocean covers more than 70% of earth surface and hosts most 300,000 described species of plants and animals to use, which
have been virtually unexploited for the development of medicines. Marine plants are the good source of biologically active
entities which exhibit therapeutic properties, when applied single or in combination of different plant extracts (polyherbal).
Polyherbal preparations are always a complex mixture of different forms and thus different compounds, which might act as agonistic,
synergistic, complementary, antagonistic or toxic way. The present study was initially carried out to test the antiplasmodial
activity of 13 mangrove plants and eight seaweeds species distributed along the coast of south India. Of these, mangrove species
Aegiceras corniculatum and the seaweed species Chaetomorpha antennina have shown maximum antiplasmodial activity. Hence, the present study was mooted out to increase the percentage of antiplasmodial
activity when applied as polyherbal preparations. The effect of marine polyherbal preparations from the methanolic extracts
of two marine plants A. corniculatum and C. antennina for their antiplasmodial activity was tested. It shows that the polyherbal extract showed 63.50 ± 0.408% suppression of parasitaemia
against Plasmodium falciparum at 1.5 mg ml−1 concentration. In vivo test was carried out with rat animal model to find out the effectiveness of the polyherbal extracts
in the live system, which reveals that polyherbal extracts have exhibited remarkable antiplasmodial activity (50.57 ± 0.465%)
against Plasmodium berghei at 120 mg kg−1 bw. This study shows that combinations of mangrove plants and seaweeds extracts had a source of lead compounds for the development
of new drugs for the treatment of malaria. 相似文献
4.
Moritz E Seidensticker S Gottwald A Maier W Hoerauf A Njuguna JT Kaiser A 《Parasitology research》2004,94(1):37-48
In the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant Plasmodium falciparum strains, in the mosquito Anopheles stephensi (Diptera: Culicidae) and in a Trypanosoma evansi clone I from strain STIB 806 K China. Recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite P. falciparum (Kaiser et al. 2001) in vitro. A comparison of agmatine efficacy with the new antimalarials artemisinin, triclosan and conventional chloroquine showed similar or even better results on the basis of growth inhibition and the reduction of developmental forms. However, no effect of triclosan or agmatine was observed at the ribonucleic acid level. In a second set of experiments, we tested the effect of 1,7-diaminoheptane and agmatine on oocyst formation in A. stephensi after infection with Plasmodium yoelii. Agmatine had an antisporozoite effect since 1,000 M led to a 59.5% inhibition of oocysts. A much weaker inhibitor of oocyst formation was 1,7-diaminoheptane. The most effective in in vitro inhibition of T. evansi was dicyclohexylamine, an inhibitor of spermidine biosynthesis with an IC50 value of 47.44 M and the deoxyhypusine inhibitor 1,7-diaminoheptane with an IC50 value of 47.80 M. However, both drugs were ineffective in in vivo experiments in a Trypanosoma mouse model. Two different spermidine analogues, 1,8-diaminooctane and 1,3-diaminopropane with IC50 values of 171 M and 181.37 M, respectively, were moderate inhibitors in vitro and ineffective in vivo. 相似文献
5.
6.
The human malarial parasite Plasmodium falciparumis responsible for an estimated 300-500 million clinical cases and 1-3 million deaths annually. At particular risk of developing severe, life-threatening malaria-associated complications are women during their first pregnancy. The observed pathologies, such as premature delivery, intrauterine growth retardation, abortion, and death of the mother and the newborn, are in large parts due to the parasite's ability to render infected erythrocytes adhesive and sequester in the intervillous space of infected placentas. In subsequent pregnancies, women are protected from maternal malaria through antibodies that prevent cytoadhesion of P. falciparum-infected erythrocytes in the placenta. Here, we summarize our current knowledge of the pathophysiological processes underpinning maternal malaria and discuss emerging concepts for intervention. 相似文献
7.
Transfection of Plasmodium falciparum has remained difficult and laborious due to a lack of suitable reporter genes and low transfection efficiency. Therefore, the luciferase gene of Renilla reniformis, a sensitive mammalian reporter gene, was evaluated as a reporter gene in this system. Our studies indicate that the R. reniformis luciferase gene can be expressed in P. falciparum and is easily detected by luminometry. P. falciparum extracts do not contain endogenous R. reniformis luciferase activity, which is essential for its use as a reporter gene in this organism. Moreover, both firefly and R. reniformis luciferase genes can be co-expressed in P. falciparum and their respective enzyme activities can be measured from the same sample. Thus, the R. reniformis luciferase gene can be used as an experimental reporter gene and/or used in conjunction with the firefly luciferase gene where one gene would be used to control transfection efficiency. The R. reniformis luciferase gene thus provides a valuable tool to facilitate transient transfection analysis in P. falciparum. 相似文献
8.
A comparative efficacy of four antibiotics, plasmocin (macrolid), Biomyc-1, -2, (tetracycline), and Biomyc-3, and Mycoplasma Removing Agent (quinolone derivatives) was determined for elimination of mycoplasma from Plasmodium falciparum culture. Presence of mycoplasma was detected using enzyme-PCR-based mycoplasma detection kit and survival of malaria parasite was determined in Giemsa's stained smear made from treated and untreated cultures. It was observed that a combination of Biomyc-1 and -2 killed malaria parasites within 24 h, whereas plasmocin and Biomyc-3 caused slow death of malaria parasite stretched over a period of 6 days. The only compound which did not kill malaria parasite and eradicated mycoplasma from P. falciparum culture was observed to be MRA. 相似文献
9.
Bardia A Tiwari SK Gunisetty S Anjum F Nallari P Habeeb MA Khan AA 《Inflammation research》2012,61(4):359-365
Objective
The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms in apoptosis and the risk of ulcerative colitis (UC). 相似文献10.
The in vitro antimalarial activity against Plasmodium falciparum and heme polymerization were evaluated for ten metalloporphyrins: gallium protoporphyrin IX (GaPPIX), sodium salt of gallium protoporphyrin IX, silver protoporphyrin IX, palladium protoporphyrin IX, cobalt protoporphyrin IX, manganese protoporphyrin IX, tin protoporphyrin IX (SnPPIX), chromium protoporphyrin IX, gallium deuteroporphyrin IX (GaDPIX) and gallium hematoporphyrin IX. Metalloporphyrins inhibited parasite growth with 50% inhibitory concentrations (IC(50)) ranging from 15.5 microM to 190 microM. In trophozoite lysate-mediated heme polymerization assays, SnPPIX, GaPPIX and GaDPIX exerted potent inhibitory activity similar to that of artemisinin and chloroquine. 相似文献
11.
Galba truncatula snails were experimentally infected with either of two different isolates of Fasciola gigantica, originating from Egypt or China, to determine the influence of these isolates on the characteristics of snail infections. The survival rates of G. truncatula on day 30 post-exposure were 90.0% and 60.2% in the Egyptian and Chinese groups, respectively. The frequency of cercaria-shedding snails within the Egyptian group was 79.8%, whereas in the Chinese group it was 22.4%. The parasite origin had a significant effect on the durations of the prepatent and patent periods. The mean number of cercariae shed from the Egyptian group was significantly greater than that shed from the Chinese group (a mean of 275.5 per cercaria-shedding snail compared with 29.0). These results could be explained by the fact that G. truncatula might be a natural intermediate host for F. gigantica in Egypt, and the greater adaptability of the Egyptian miracidia of F. gigantica to unusual snail hosts. These results demonstrate the influence of the geographic origin of the parasite on the success of trematodes infecting snails. 相似文献
12.
Karina?M.?Rebello Luzia?M.?C.?C?rtes Bernardo?A.?S.?Pereira Bernardo?M.?O.?Pascarelli Suzana?C?rte-Real Léa?C.?Finkelstein Rosa?T.?Pinho Claudia?M.?d’Avila-Levy Carlos?R.?Alves 《Parasitology research》2009,106(1):95-104
Leishmania (Viannia) braziliensis is the major causative agent of American tegumentary leishmaniasis, a disease that has a wide geographical distribution and
is a severe public health problem. The cysteine proteinase B (CPB) from Leishmania spp. represents an important virulence factor. In this study, we characterized and localized cysteine proteinases in L. (V.) braziliensis promastigotes. By a combination of triton X-114 extraction, concanavalin A-affinity, and ion exchange chromatographies, we
obtained an enriched fraction of hydrophobic proteins rich in mannose residues. This fraction contained two proteinases of
63 and 43 kDa, which were recognized by a CPB antiserum, and were partially sensitive to E-64 in enzymatic assays with the
peptide Glu-Phe-Leu. In confocal microscopy, the CPB homologues localized in the peripheral region of the parasite. This data
together with direct agglutination and flow cytometry assays suggest a surface localization of the CPB homologues. The incubation
of intact promastigotes with phospholipase C reduced the number of CPB-positive cells, while anti-cross-reacting determinant
and anti-CPB antisera recognized two polypeptides (63 and 43 kDa) derived from phospholipase C treatment, suggesting that
some CPB isoforms may be glycosylphosphatidylinositol-anchored. Collectively, our results suggest the presence of CPB homologues
in L. braziliensis surface and highlight the need for further studies on L. braziliensis cysteine proteinases, which require enrichment methods for enzymatic detection. 相似文献
13.
In Lambaréné (Gabon), where a high level of Plasmodium falciparum resistance to chloroquine has been reported, we assessed the relationship between polymorphisms in the P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug resistance-1 (Pfmdr1) genes and the clinical severity of malaria. Ninety-one and 60 P. falciparum isolates from children with uncomplicated or severe malaria were collected in 1996 and 2002, respectively. Single nucleotide
mutations at codon 76 in the Pfcrt gene and at codons 86, 184, 1034, 1042, and 1246 in the Pfmdr1 gene were assessed by PCR-RFLP. All P. falciparum isolates presented the Pfcrt K76T mutation, whatever the clinical status. A high prevalence (>80%) of the Pfmdr1 86Tyr and 184Phe mutations was detected at both time points and in both clinical groups. We did not identify any specific
mutation in the Pfmdr1 gene associated with the severity of disease, and the multiplicity of P. falciparum infection was also similar in both groups. Our results showed no change in the polymorphism of Pfcrt and Pfmdr1 genes in P. falciparum isolates collected in 1996 and 2002, and the severity of the disease was not associated with specific mutations neither in
the Pfcrt nor in the Pfmdr1 genes in the study site. 相似文献
14.
15.
The var-gene encoding Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is known to play a major role in the pathogenicity of the P. falciparum parasite. The protein enables the parasite to adhere to the endothelial linings of small blood vessels (cytoadherence) as
well as to non-infected erythrocytes (rosetting), thus preventing clearance from the bloodstream. The development and spread
of resistance towards most anti-malarial drugs used for treatment and prevention of the most severe form of malaria truly
emphasise the importance of a continuous research and development of new drugs. In this study we use Systematic Evolution
of Ligands by EXponential enrichment (SELEX) methodology to isolate high-affinity ligands (aptamers). To validate the results
from the SELEX in vitro selection, different aptamers have been selected against PfEMP1 in a live cell assay of P. falciparum strain FCR3S1.2, a highly rosetting strain. We have been able to show the rosette disrupting capacity of these SELEX-aptamers
at concentrations of 33 nM and with 100% disruption at 387 nM. The described results show that RNA aptamers are promising
candidates for adjunct therapy in severe malaria. 相似文献
16.
17.
Mara A. Correa Tatiane Canhamero Andrea Borrego Iana S. S. Katz José R. Jensen José Luiz Guerra Wafa H. K. Cabrera Nancy Starobinas Jussara G. Fernandes Orlando G. Ribeiro Olga M. Ibañez Marcelo De Franco 《Inflammation research》2017,66(11):969-980
Objective and design
Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA.Treatment
Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days.Results
AIRmax SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H2O2, NO, IL-1β, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development.Conclusion
Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.18.
19.
Esters of amino acids are known to penetrate into cells by simple diffusion. Subsequently, they are hydrolyzed by hydrolases to release the parent amino acid. Due to the abundance of hydrolases in phagolysosomes, amino acids accumulate, there because the rate of influx and hydrolysis exceed the rate of amino acid efflux through specific carriers. The osmotic effect of this accumulation results in the disruption of the organelles. This mechanism has been demonstrated to be responsible for the killing of Leishmania amastigotes by amino acid esters. In this investigation, it is shown that all esters tested, including alcohol esters, N-acetyl esters and the esters of some dipeptides, inhibit the growth of Plasmodium falciparum in culture. Inhibition is time-dependent and, in some cases, ring-stage parasites are more sensitive than trophozoites. Similar to the findings with Leishmania, alcohol esters of Glu, Leu, Met, Phe and Trp are more toxic to Plasmodium whereas Ala, Gly, His and Ile are much less noxious. Esters caused the release of acridine orange that selectively accumulates in the phagolysosome-like food vacuole of the parasite, attesting the ostensible destruction of this organelle by osmotic lysis. The toxicity of the N-acetyl esters is probably associated in part to their ability to inhibit cytosolic proteases. Since excess of amino acids can also inhibit proteolysis, the effect of free amino acids on parasite growth was also tested. Of the 19 odd amino acids tested, only three, namely Cys, His and Trp, were found to be toxic to the parasites at millimolar concentrations and the reasons for their possible specific toxicity are discussed. 相似文献
20.
Bilen MF Pilloff MG Belaich MN Da Ros VG Rodrigues JC Ribeiro BM Romanowski V Lozano ME Ghiringhelli PD 《Virus genes》2007,35(3):549-562
We have located and cloned the Anticarsia gemmatalis multicapsid nucleopolyhedrovirus isolate 2D (AgMNPV-2D) genomic DNA fragment containing the immediate early 1 ORF and its flanking regions. Computer assisted analysis of the complete ie1 locus nucleotide sequence information was used to locate regulatory signals in the upstream region and conserved nucleotide and
amino acid sequences. Comparative studies led to the identification of several characteristic protein motifs and to the conclusion
that AgMNPV-2D is more closely related to Choristoneura fumiferana defective NPV than to other Group I nucleopolyhedrovirus. We have also shown that the AgMNPV IE1 protein was able to transactivate an early Autographa californica MNPV promoter and its own promoter in transient expression assays. In order to investigate the biological functionality of
the ie1 promoter, the ie1 upstream activating region (UAR) was molecularly dissected and cloned upstream of the E. coli
lacZ ORF. The results obtained, after transfection of UFL-AG-286 insect cells, leading us to find that the −492 and −357 versions
contains sequence motifs important for the level of the lacZ reporter gene expression.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.
The GenBank accession number of the sequence reported in this paper is AF368905. 相似文献