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Results for “Plasmodium knowlesi”

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PubMed1980

Factors affecting the ability of isolated Plasmodium knowlesi merozoites to attach to and invade erythrocytes.

Plasmodium knowlesi merozoites were prepared by the polycarbonate sieving method of Dennis, Mitchell, Butcher & Cohen (1975). Merozoite function was assayed by their attachment to and invasion of rhesus erythrocytes at 37 degrees C. The early merozoites from the culture chamber were the most invasive, although maximum numbers of merozoites appeared later. Merozoites were most stable when incubated at room temperature (23 degrees C). At 37 and 0 degrees C invasiveness rapidly declined to zero. Attachment was rapidly lost at 37 degrees C but was retained at 0 degrees C. Attachment was unchanged in the pH range 6.8--7.9 but invasion was reduced at pH 7.9. The presence of L-fucose, D-galactose, D-glucose, D-mannose, N-acetyl-D-galactosamine or N-acetyl-D-glucosamine did not reduce invasion. Attachment and invasion were greatly reduced or abolished by the presence of 2.5 mM EDTA or EGTA, by lactoperoxidase-catalysed iodination of the merozoites, or by treatment of the merozoites with trypsin at a concentration of 1 micrograms/ml or greater for 10 min at 23 degrees C.

Animals↗

PubMed1974

In vitro antimalarial activity of nucleic acid precursor analogues in the simian malaria Plasmodium knowlesi.

Analogues of nucleic acid precursors were screened for antimalarial activity in Plasmodium knowlesi by using an in vitro culture system. Activity was assessed by the degree of inhibition of incorporation of l-[methyl-(14)C]methionine into protein and of [8-(14)C]adenosine and [6-(14)C]orotic acid into ribonucleic acid and deoxyribonucleic acid. The incorporation of adenosine or orotic acid was effectively inhibited by many of the compounds, including 3' analogues of purine nucleosides, many of the 6-position analogues of purine bases and nucleosides, and 5-position analogues of orotic acid. Only a few compounds inhibited methionine incorporation into protein, and in each instance adenosine or orotic acid incorporation also was inhibited. Some compounds inhibited adenosine or orotic acid incorporation into both ribonucleic acid and deoxyribonucleic, whereas other analogues inhibited incorporation into one nucleic acid only. The qualitative and quantitative differences suggest that this experimental system may be appropriate for investigation of metabolic pathways of the malaria parasite, as well as for demonstration of antimalarial activity of candidate antimalaria drugs.

Animals↗

PubMed1977

A review of metozoite vaccination against Plasmodium knowlesi malaria.

Techniques for the isolation of merozoites of Plasmodium knowlesi malaria have allowed their use in experimental vaccines. Rhesus monkeys were protected to a very great extent from otherwise lethal challenge with this malaria when Freund's Complete Adjuvant was a vaccine component.

Animals↗

PubMed1990

In vitro maturation of the exoerythrocytic stage of Plasmodium knowlesi observed under phase contrast microscopy.

Exoerythrocytic stages of Plasmodium knowlesi were obtained in primary culture of rhesus monkey hepatocytes. The development of a single parasite was followed with phase contrast microscopy until release of merozoites in slightly less than 5 days. This direct observation may offer opportunities to determine visually factors that may influence specific steps of schizont development.

Animals↗

PubMed2004

Naturally acquired Plasmodium knowlesi malaria in human, Thailand.

We describe a case of naturally acquired infection with Plasmodium knowlesi in Thailand. Diagnosis was confirmed by the small subunit ribosomal RNA and the mitochondrial cytochrome b sequences. The occurrence of simian malaria in human has signified the roles of wild primate populations in disease transmission in some malaria-endemic areas.

Adult↗

PubMed1996

Plasmodium knowlesi: secondary processing of the malaria merozoite surface protein-1.

Secondary processing of the Plasmodium falciparum malaria merozoite surface protein-1 (MSP-1) is defined as a single proteolytic cleavage within the carboxy-terminal membrane-bound component of the MSP-1 protein complex on the free merozoite surface. The N-terminal cleavage product (MSP-1(33)) is shed from the parasite surface along with a number of other polypeptides, whereas the C-terminal processing product remains bound to the merozoite surface and is the only part of MSP-1 detectable in the newly invaded host cell. We report that secondary processing of MSP-1 takes place in a similar manner on invasive merozoites of the simian malaria parasite Plasmodium knowlesi. Processing can take place to a limited extent in pure isolated merozoites; however, within 10 min of the addition of purified invasive merozoites to rhesus erythrocytes, processing and shedding of MSP-1 has gone to completion only in those parasites which have undergone invasion; residual free merozoites remain uniformly reactive with antibodies against MSP-1(33). Successful invasion is therefore associated with complete shedding of MSP-1(33) from the merozoite surface. The nucleotide sequence of the 3' domain of the P. knowlesi MSP-1 gene is also presented.

Amino Acid Sequence↗

PubMed1978

Antigenic analysis of sequential erythrocytic stages of Plasmodium knowlesi.

The antigenic composition of sequential erythrocytic stages of Plasmodium knowlesi has been compared by crossed immuno-electrophoresis using a pool of immune rhesus monkey antiserum. Eleven major parasite antigens have been identified; 9 are stage-independent, and 2 stage-dependent. Differences in the relative amount of the stage-independent antigens have been demonstrated and quantified. The distribution of antigens between parasites and schizont and infected red cell membranes has been examined. Only 6 of the 11 parasite antigens were exhibited by a schizont membrane preparation, all these antigens were also expressed by the intracellular parasite. Antigens exclusive to the schizont membrane were not demonstrated.

Animals↗

PubMed1978

Malaria immunization in Rhesus monkeys. A vaccine effective against both the sexual and asexual stages of Plasmodium knowlesi.

Rhesus monkeys were immunized with a preparation of Plasmodium knowlesi parasites containing principally microgametes with lesser numbers of macrogametes and asexual trophozoites. The antigen mixture was emulsified in Freund's complete adjuvant (FCA) and administered intramuscularly. After one or two inoculations of from 10(5) to 10(7) microgametes in FCA, monkeys showed high levels of circulating anti-gamete antibodies as demonstrated by various in vitro microgamete immobilization or transmission blocking tests. After challenge with P. knowlesi, immunized monkeys developed low level asexual parasitemias and were not infectious to feeding mosquitoes as measured by growth of the parasite on the mosquito gut. Control monkeys developed rapidly rising, usually fatal infections and were highly infectious to mosquitoes. Anti-gamete antibodies appear to neutralize the sexual parasites and prevent mosquito infection within the gut of the recently fed mosquito vector. Suppression of asexual parasitemia in immunized monkeys may be due to the presence of asexual trophozoites in the antigen mixture or to antigens common to both sexual and asexual stages of the parasite. A vaccine effective as a single injection capable of interrupting malaria transmission from man to man whereas reducing the severity of the disease in infected individuals offers a new approach to the control of one of the major diseases affecting man.

Animals↗

PubMed1985

Immunochemical analysis of surface membrane antigens on erythrocytes infected with non-cloned SICA[+] or cloned SICA[-] Plasmodium knowlesi.

The SICA[-] or non-agglutinable phenotype of Plasmodium knowlesi schizont-infected erythrocytes has been defined serologically but not biochemically. Similarly, non-cloned SICA[+] or agglutinable parasites have been shown serologically to express SICA or variant antigen(s) but the number and nature of such antigens have not been defined. Here we describe the immunochemical analysis of surface antigen expression on [125I]lactoperoxidase-labelled erythrocytes infected either with a SICA[-] clone or with non-cloned SICA[+] parasites using the methods developed for identification of variant antigens with cloned SICA[+] parasites. No 125I-labelled antigens in the size range Mr 190 000-225 000 were specifically immunoprecipitated from erythrocytes infected with the SICA[-] clone, even using homologous antisera produced by multiple infections or immunizations. Further, no 125I-labelled proteins of this size were seen in detergent extracts of the SICA[-] parasites that were not also seen with uninfected cells. We conclude that the SICA[-]phenotype reflects the absence of a variant antigen at the erythrocyte surface, as predicted by the serological assays. In contrast, with the non-cloned SICA[+] parasites, a complex group of proteins, Mr 195 000-225 000, was identified by [125I]lactoperoxidase labelling of intact infected erythrocytes. These proteins are SICA antigens since they not only share the characteristic detergent solubility properties and size range of SICA antigens identified previously with SICA[+] clones, but they were only immunoprecipitated by antisera which reacted specifically with the surface of infected erythrocytes. Agglutinating sera immunoprecipitated several of these 125I-labelled antigens. Sera specific for clones derived from this non-cloned SICA[+] population failed to agglutinate, but did react by indirect immunofluorescence with 10-16% of infected cells. These sera specifically immunoprecipitated single, quantitatively minor 125I-labelled antigens in this size range. The results suggest that a population of non-cloned SICA[+] parasites contains at least 10 different variant-antigen phenotypes. Indirect immunofluorescence was also performed against a non-cloned SICA[+] population derived by antigenic variation of a SICA[+] clone in vivo. The variant population contained at least 3 antigenically distinct SICA phenotypes, indicating that antigenic variation of clones may produce populations as antigenically heterogenous as antigenic variation of uncloned lines. It is therefore likely that natural malaria isolates contain a large number of different variant antigens.

Agglutination↗

PubMed2004

A SICAvar switching event in Plasmodium knowlesi is associated with the DNA rearrangement of conserved 3' non-coding sequences.

Plasmodium knowlesi variant antigens are expressed at the surface of infected erythrocytes and are encoded by the Schizont Infected Cell Agglutination variant antigen (SICAvar) multigene family. The 3' region of the SICAvar gene locus encoding the 205 kDa variant antigen expressed in the Pk1(B+)1+ parasites was found to be altered compared to the Pk1(A+) parental clone. Here we report that this alteration is the result of a DNA rearrangement and that the original and altered 205 SICAvar alleles appear to encode bona fide variant antigens. Importantly, 205A and 205B SICAvar RNA sequences are detectable in similar apparent quantities as determined by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) amplification experiments. However, expression of the 205 kDa SICA protein at the surface of the infected erythrocyte is not characteristic of the Pk1(A+) parasites and the 205 SICAvar transcript has not been detected in Pk1(A+) parasites by northern blot analysis. Furthermore, we report that many distinct SICAvar transcripts were detected in P. knowlesi Pk1(B+)1+ cDNA library hybridization screens. Of special interest, in light of these data, distinctive differences at the 3' end of the 205A and 205B alleles are observed, which may be of functional importance. An analysis of the 3' untranslated region (UTR) of SICAvar genes in more than 100 sequences revealed a surprising common sequence pattern characterized by blocks of imperfect, GT-rich, heptad repeated motifs (Block I), followed by A and T rich homopolymers (Block II) and in a large number of genes, GC-rich segments (Block III). We show that this region undergoes extensive recombination and that the preferential stability of the 205 SICAvar transcript in Pk1(B+)1+ parasites may be associated with the presence of its specific Block III sequences. We speculate that the conserved yet polymorphic SICAvar 3'UTR sequences, and comparable regions in P. falciparum var genes, function in the stage-specific and developmentally regulated post-transcriptional gene silencing (PTGS) of variant antigen transcripts.

3' Untranslated Regions↗

PubMed1985

Inability of Plasmodium knowlesi sporozoites to invade Anopheles freeborni salivary glands.

Oocysts of Plasmodium knowlesi developed normally on the gut of the mosquito Anopheles freeborni, rupturing and releasing sporozoites at 10-14 days post-infection. Subsequently, however, sporozoites were never found in this mosquito's salivary glands. Heterologous transplants of whole salivary glands from uninfected An. freeborni and An. dirus, a completely susceptible mosquito, into the abdomens of insects heavily infected with mature oocysts were done. Sporozoites failed to infect An. freeborni glands implanted in An. dirus but did enter An. dirus glands implanted in An. freeborni. These experiments suggest that P. knowlesi sporozoites are unable to recognize An. freeborni glands.

Animals↗

PubMed2001

Histopathological changes of Macaca mulatta infected with Plasmodium knowlesi.

OBJECTIVE: To study the histopathological changes of relevant internal organs of Macaca mulatta infected with Plasmodium knowlesi (P. knowlesi). METHODS: Histopathological examination of 3 monkeys who died of P. knowlesi infection, 2 P. knowlesi infected monkeys who died of treatment failure with artesunate suppository and 1 P. knowlesi infected monkey that was cured by piperaquine phosphate (PQP) but died of trauma and necrosis of the fore limb. RESULTS: The heart, liver, spleen, lung, kidney, brain, pancreas, parathyroid, pituitary and lymph nodes showed severe pathological changes in 3 monkeys (No. 1, 7 and 12) who died of P. knowlesi infection and 1 infected monkey (No. 72) who died of treatment failure with artesunate suppository. Red blood cells containing malarial parasites and pigments were concentrated in the capillaries of these organs. Malarial pigments were deposited in many organs or phagocytized by macrophages in 1 monkey (No. 131), it was cured by piperaquine phosphate but died of trauma and necrosis of the fore limb; cellular atrophy and disappearance of pancreatic islets, parathyroid and pituitary cells were also observed. One monkey (No. 33) treated with artesunate suppository, showed that blood parasites became negative but recrudesced and pituitary later died from a gavage accident. Its organs showed a significant difference to those of the infected monkeys receiving no treatment. Only the liver Kupffer cells and cerebral matrix contained malarial parasites and pigments; many relevant internal organs showed repair. CONCLUSION: The pathological changes of relevant internal organs of Macaca mulatta infected with P. knowlesi were examined in detail, especially cellular atrophy and the disappearance of pancreatic islets, parathyroid and pituitary cells and myolysis of cardiac muscles. These changes have not previously been reported elsewhere.

Animals↗

PubMed1986

Lipidic vacuoles in Plasmodium knowlesi erythrocytic schizonts.

Electron microscopy of schizont development in erythrocytic Plasmodium knowlesi has revealed that spheroidal vacuoles 250 nm in diameter with semi-dense contents appear at the periphery of the parasite prior to the budding of merozoites. When treated with non-polar solvents, their contents are completely extracted, and after fixation in tannic-glutaraldehyde they contain regular lamellae with a periodicity of 5.5 nm. Both of these reactions are typical of lipids. Some of these structures are associated with phagosomal vacuoles which may contribute to their lamellae. They disappear at the onset of merozoite formation, but membranous whorls of various sizes continue to be associated with the schizont surface during budding of merozoites. It is suggested that the lipidic vacuoles are a source of preformed lipid which can be utilized rapidly during the generation of merozoites.

Animals↗

PubMed1990

The Duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites.

Plasmodium vivax and Plasmodium knowlesi merozoites invade human erythrocytes that express Duffy blood group surface determinants. A soluble parasite protein of 135 kd binds specifically to a human Duffy antigen. Using antisera affinity purified on the 135 kd protein, we cloned a gene that encodes a member of a P. knowlesi family of erythrocyte binding proteins. The gene is a member of a family that includes three homologous genes located on separate chromosomes. Two genes are expressed as major membrane-bound products that give rise to soluble erythrocyte binding proteins: the 135 kd Duffy binding protein and a 138 kd protein that binds only rhesus erythrocytes. These different erythrocyte binding specificities may result from sequence divergence of the homologous genes. The Duffy receptor family is localized in micronemes, an organelle found in all organisms of the phylum Apicomplexa.

Amino Acid Sequence↗

PubMed1987

Cloning and characterization of an abundant Plasmodium knowlesi antigen which cross reacts with Gambian sera.

A 110 kDa Plasmodium knowlesi antigen, termed PK110, has been identified on the basis of messenger RNA abundance in late schizonts. Most Plasmodium genes previously cloned have been identified by immune sera, which have selected immunodominant antigens composed of repeating epitopes. Although PK110 was not selected by immune sera, it also contains amino acid repeats, indicating that this structure may be a common feature of malarial proteins. Determination of 296 codons in the PK110 gene revealed the presence of thirteen tandem repeats of twelve amino acids whose consensus sequence is E E T Q K T V E P E Q T. A termination codon interrupts the fourteenth repeat, indicating that these repeats are at the C-terminus of the protein. Indirect immunofluorescence experiments with sera raised against the lambda gt11 fusion protein indicate that PK110 is present in intra-erythrocytic late schizonts. Cloned PK110 is recognized by Gambian sera, and shares epitopes with Plasmodium ovale. PK110 does not cross react immunologically or by DNA hybridization with Plasmodium falciparum.

Amino Acid Sequence↗

PubMedDate not supplied

The fine structure of secretion by Plasmodium knowlesi merozoites during red cell invasion.

The secretory organelles of Plasmodium knowlesi were studied ultrastructurally to examine their mode of action during invasion. The formation of lamellar structures in merozoite rhoptries within late stage schizonts is prevented by the protease inhibitors chymostatin and leupeptin. Under normal conditions vesicles lined by 6-nm membranes are formed in rhoptries during erythrocyte invasion. Stereoscopic viewing of tilted sections shows that where the merozoite apex contacts the parasitophorous vacuole (PV) membrane during invasion, a domed elevation of the PV surface lies within the mouth of the rhoptry duct in contact with the secretory matrix. The membrane of the early invasion pit is thinner (6 nm) than the red cell membrane elsewhere, and sheets of lamellar material are frequently present on the invasion pit surface. These findings support the proposal that the rhoptry-microneme complex is capable of generating membranous material and inserting it into the red cell surface in a controlled manner to create the parasitophorous vacuole. On the basis of this model, measurements from serial sections show that the rhoptries could provide enough material to create a membrane lining the parasitophorous vacuole, and, with the contribution of the microspheres, could double it to accommodate the early ring stage of the parasite.

Animals↗

PubMed1998

Characterisation of the Cdc2-related kinase 2 gene from Plasmodium knowlesi and P. berghei.

The complete sequence of the cdc2-related kinase 2 (CRK2) gene from Plasmodium knowlesi and from P. berghei was determined. In both species, the CRK2 gene is closely linked to an elongation factor 1 alpha gene. The two CRK2 proteins are highly homologous to the P. falciparum PfPK5 protein. The CRK2 gene of both species is expressed at a low level during the asexual cell-cycle within the host erythrocytes. The P. berghei CRK2 mRNA is also present in gametocytes and in stages during development in the mosquito, suggesting a role of this protein in different parts of the life cycle. A conserved sequence located in the 5' untranslated region immediately upstream of the initiator ATG has the potential to form a stem-loop structure. Although the CRK2 protein possesses most of the domains that are conserved among cdc2-proteins, neither a recombinant P. knowlesi CRK2 protein nor a recombinant P. berghei protein was able to complement a yeast cdc28ts mutant. Furthermore and in contrast to the P. falciparum PfPK5 protein, a recombinant monomeric P. knowlesi CRK2 protein showed no kinase activity.

Amino Acid Sequence↗

PubMed1994

Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion.

Plasmodium vivax and the related monkey malaria, P. knowlesi, require interaction with the Duffy blood group antigen, a receptor for a family of chemokines that includes interleukin 8, to invade human erythrocytes. One P. vivax and three P. knowlesi proteins that serve as erythrocyte binding ligands in such interactions share sequence homology. Expression of different regions of the P. vivax protein in COS7 cells identified a cysteine-rich domain that bound Duffy blood group-positive but not Duffy blood group-negative human erythrocytes. The homologous domain of the P. knowlesi proteins also bound erythrocytes, but had different specificities. The P. vivax and P. knowlesi binding domains lie in one of two regions of homology with the P. falciparum sialic acid binding protein, another erythrocyte binding ligand, indicating conservation of the domain for erythrocyte binding in evolutionarily distant malaria species. The binding domains of these malaria ligands represent potential vaccine candidates and targets for receptor-blockade therapy.

Animals↗