PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Plasmodium knowlesi”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1997

Cloning and cross-species comparison of the thrombospondin-related anonymous protein (TRAP) gene from Plasmodium knowlesi, Plasmodium vivax and Plasmodium gallinaceum.

To examine the structure of the Plasmodium sporozoite micronemal protein, thrombospondin-related anonymous protein (TRAP) we have isolated TRAP genes from three species of Plasmodium: P. gallinaceum (PgTRAP), P. knowlesi (PkTRAP) and P. vivax (PvTRAP). Thus it is now possible to compare the TRAP gene from a total of six species of Plasmodium. The overall structure of TRAP is conserved in all species; specifically, an amino-terminal A-domain similar to magnesium-binding domains of mammalian integrins; a thrombospondin-like sulfatide-binding domain similar to region II in Plasmodium circumsporozoite protein; an acidic asparagine/proline-rich repeat region; a trans-membrane domain and a short acidic cytoplasmic region with a highly conserved carboxy terminus. The overall structure of TRAP from P. gallinaceum and P. falciparum (PfTRAP) is conserved and phylogenetic analysis suggests a monophyletic relationship of avian P. gallinaceum and human P. falciparum. Comparison of the amino acid sequences of the A-domain of PgTRAP and PfTRAP indicates a more rapid divergence of this domain with respect to the rest of the protein in these two species. The structural differences of PgTRAP and PfTRAP may relate to the distinct invasion pathways, macrophage and endothelial cell invasion of P. gallinaceum sporozoites versus hepatocyte invasion of P. falciparum.

Amino Acid Sequence↗
PubMed2002

Comparative characterization of hexose transporters of Plasmodium knowlesi, Plasmodium yoelii and Toxoplasma gondii highlights functional differences within the apicomplexan family.

Chemotherapy of apicomplexan parasites is limited by emerging drug resistance or lack of novel targets. PfHT1, the Plasmodium falciparum hexose transporter 1, is a promising new drug target because asexual-stage malarial parasites depend wholly on glucose for energy. We have performed a comparative functional characterization of PfHT1 and hexose transporters of the simian malarial parasite P. knowlesi (PkHT1), the rodent parasite P. yoelii (PyHT1) and the human apicomplexan parasite Toxoplasma gondii ( T. gondii glucose transporter 1, TgGT1). PkHT1 and PyHT1 share >70% amino acid identity with PfHT1, while TgGT1 is more divergent (37.2% identity). All transporters mediate uptake of D-glucose and D-fructose. PyHT1 has an affinity for glucose ( K (m) approximately 0.12 mM) that is higher than that for PkHT1 ( K (m) approximately 0.67 mM) or PfHT1 ( K (m) approximately 1 mM). TgGT1 is highly temperature dependent (the Q (10) value, the fold change in activity for a 10 degrees C change in temperature, was >7) compared with Plasmodium transporters ( Q (10), 1.5-2.5), and overall has the highest affinity for glucose ( K (m) approximately 30 microM). Using active analogues in competition for glucose uptake, experiments show that hydroxyl groups at the C-3, C-4 and C-6 positions are important in interacting with PkHT1, PyHT1 and TgGT1. This study defines models useful to study the biology of apicomplexan hexose permeation pathways, as well as contributing to drug development.

Amino Acid Sequence↗
PubMed1979

Factors affecting the in vitro culture of Plasmodium falciparum and Plasmodium knowlesi.

Plasmodium falciparum and Plasmodium knowlesi have been established in continuous culture using the basic method of Trager & Jensen. Various parameters of the culture system have been examined, namely, the gas requirements, serum and red cell requirements, frequency of medium replacement, and a comparison of static and agitated cultures made. The most important factors affecting growth in vitro seem to be the oxygen tension, red cell concentration, the frequency with which old medium is replaced, and the use of appropriate sera. Preliminary results indicate that horse serum may be possible as a replacement for human serum. Initial studies with P. knowlesi indicate that in the course of adapting to culture, parasites may change their antigenic specificity.

Animals↗
PubMed2003

Phylogenetic analysis of CSP and MSP-9 gene sequences demonstrates the close relationship of Plasmodium coatneyi to Plasmodium knowlesi.

Plasmodium coatneyi is a simian malaria parasite with various biological features similar to the human malaria P. falciparum and potential as a model for severe cases of malaria. We have characterized two single-copy genes from P. coatneyi, the circumsporozoite protein and merozoite surface protein-9 genes, and determined its phylogenetic relationship among Plasmodium species. This study demonstrates that while it has similarities to P. falciparum, P. coatneyi belongs to a distant clade including several simian malaria parasites and the human malaria P. vivax. P. coatneyi forms a monophyletic group with P. knowlesi, demonstrating their close relationship despite some very distinctive biological characteristics.

Amino Acid Sequence↗
PubMed1982

Immunogenic antigens common to Plasmodium knowlesi and Plasmodium falciparum are expressed on the surface of infected erythrocytes.

Sera of Gambian individuals and rhesus monkeys immune against infections with Plasmodium falciparum and plasmodium knowlesi, respectively, were reacted with triton X-100-solubilized membranes of infected erythrocytes. Indirect immune precipitation with Staphylococcus aureus, Cowan strain A, followed by dodecylsulfate-polyacrylamide gel electrophoresis, were used to identify interspecies plasmodial antigens that were immunogenic in vivo. Both types of sera specifically precipitated Plasmodium-specific antigens with Mrs of 125,000, 90,000, and 65,000 to 50,000 from membranes of P. knowlesi-infected erythrocytes that had been labeled with 125I using the lactoperoxidase-catalyzed radioiodination or metabolically with 14C-amino acids. In addition, P. falciparum inhibited the precipitation of P. knowlesi antigens by the Gambian immune sera. Our results indicate, that during erythrocytic schizogony, interspecies Plasmodium antigens are exposed on the surfaces of infected erythrocytes.

Animals↗
PubMed1983

Resistance of Melanesian elliptocytes (ovalocytes) to invasion by Plasmodium knowlesi and Plasmodium falciparum malaria parasites in vitro.

Erythrocytes from humans with Melanesian elliptocytosis are resistant to invasion by Plasmodium falciparum in vitro and epidemiological evidence suggests they may be resistant to P. vivax and P. malariae. We have examined the ability of P. knowlesi merozoites to invade Melanesian elliptocytes in vitro as a definitive means of examining these cells for resistance to invasion by malarial species with different receptor requirements. The Melanesian elliptocytes were highly resistant to invasion by P. knowlesi merozoites showing that the resistance associated with this erythrocyte variant lies at a level common to the invasion pathway(s) of P. falciparum and P. knowlesi. This makes Melanesian elliptocytosis unique as no other human erythrocyte variant has been shown to be resistant to invasion by both species.

Elliptocytosis, Hereditary↗
PubMed1997

Characterization of simian malarial parasite (Plasmodium knowlesi)-induced putrescine transport in rhesus monkey erythrocytes. A novel putrescine conjugate arrests in vitro growth of simian malarial parasite (Plasmodium knowlesi) and cures multidrug resistant murine malaria (Plasmodium yoelii) infection in vivo.

A stage-dependent increase in the level of putrescine, spermidine, and spermine during intraerythrocytic growth of Plasmodium knowlesi in rhesus monkey erythrocytes was observed. Further, intraerythrocytic P. knowlesi-induced putrescine influx was found in trophozoite stage-infected erythrocytes and process was time- and temperature-dependent and showed saturable kinetics. Characteristics of induced putrescine influx appears in infected erythrocytes to be close to the normal erythrocytes in terms of affinity of putrescine to the putrescine transporter (Km 34.6 +/- 3.8 microM as normal erythrocytes and Km 37.2 +/- 5.2 microM in infected erythrocytes). However, the difference involves the significant increase in the putrescine influx rate after infection (Vmax = 4.21 nmol/min/10(10) normal erythrocytes, compared with 11.6 nmol/min/10(10) infected erythrocytes). Energy dependence, involvement of -SH group, and noninterference by amino acid, spermidine, and spermine in the putrescine influx process clearly demonstrate the presence of a distinct transporter for putrescine in infected erythrocytes. A putrescine conjugate N1,N4-bis(7-chloroquinoline-4-yl)butane-1, 4-diamine (BCBD) was synthesized, which inhibits the putrescine influx in the P. knowlesi infected erythrocytes (Ki of 43.2 microM) as well as in vitro growth of P. knowlesi (IC50 value, 7.64 +/- 0.97 ng/ml BCBD, 10.8 +/- 0.45 ng/ml chloroquine). Addition of exogenous polyamines failed to reverse the inhibitory effect of BCBD in vitro. Administration of BCBD (24 mg/kg body weight, intraperitoneal, twice a day for 4 days) cured the Swiss mice infected with multidrug-resistant infection of Plasmodium yoelii. Therefore, inhibition of putrescine transport in malaria-infected erythrocytes offers a lead in the search of a new class of chemotherapeutic molecules against malaria.

Aminoquinolines↗
PubMed1985

Multiple non-repeated epitopes on the circumsporozoite protein of Plasmodium knowlesi.

The Plasmodium knowlesi circumsporozoite (CS) protein contains a repetitive immunodominant epitope. Here we show that the serum of rabbits repeatedly immunized with P. knowlesi sporozoites contains antibodies which bind to immobilized synthetic peptides ('C2', 'N2', and 'charged') representing two different polar regions of the CS polypeptide. These reactions are specific since the binding is inhibited only by the homologous peptides. Antisporozoite antibodies were isolated from the rabbit serum by affinity chromatography on Sepharose beads coupled to two synthetic peptides, 'C2' and 'charged'. Both purified antibodies recognized the CS protein and the intracellular precursors as shown by Western blotting analysis using sporozoite extracts. These results demonstrate that the corresponding areas of the native CS molecule are immunogenic, accessible to interaction with antibody, and therefore constitute potential targets for vaccine development. In addition, the present findings confirm the published amino acid sequence of a large portion of the CS protein which has been deduced from the nucleotide sequence of the corresponding gene.

Amino Acid Sequence↗
PubMed1980

Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts.

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.

Animals↗
PubMedDate not supplied

Antibodies to lactate dehydrogenase of Plasmodium knowlesi are specific to Plasmodium species.

Polyclonal immune monkey serum raised against schizonts of Plasmodium knowlesi (H-strain) showed the presence of antibodies to lactate dehydrogenase (LDH) of P. knowlesi by immunodot enzyme staining method. The anti-LDH antibodies are most probably directed towards an epitope distinct from the catalytic site as shown by the specific enzyme staining of LDH after binding with antibody on nitrocellulose paper. These antibodies showed reactivity with LDH from different strains (H, P and W1 strains of P. knowlesi) and species (P. cynomolgi B, P. berghei, P. yoelii, P. falciparum and P. vivax) of malarial parasites but did not cross-react with three isoenzymic forms of mammalian LDH (A4, B4 and C4) as well as with LDH from some protozoan and helminth parasites. These findings suggest that the anti-LDH antibodies have defined specificity to Plasmodium spp.

Animals↗
PubMed2004

New selectable markers and single crossover integration for the highly versatile Plasmodium knowlesi transfection system.

Plasmodium knowlesi provides a highly versatile transfection system for malaria, since it enables rapid genetic modification of the parasite both in vivo as well as in vitro. However, it is not possible to perform multiple genetic manipulations within one parasite line because of a lack of selectable markers. In an effort to develop additional selectable markers for this parasite, positive and negative selectable markers that have recently been successfully used in Plasmodium falciparum were tested. It was shown that the positive selectable markers human dihydrofolate reductase (hdhfr), blasticidin S deaminase (bsd) and neomycin phosphotransferase II (neo) all conferred drug resistance to P. knowlesi when introduced as episomes. The plasmid containing the hdhfr selectable marker was not only successfully introduced as circular form, but also as linear fragment, demonstrating for the first time single crossover integration in P. knowlesi. Thymidine kinase was tested for its potential as negative selectable marker and it was shown that recombinant P. knowlesi parasites expressing thymidine kinase from episomes were highly sensitive to ganciclovir compared to wild-type P. knowlesi. The availability of new positive selectable markers and a strong candidate for a negative selectable marker for P. knowlesi, in combination with the opportunity to perform targeted single crossover integration in P. knowlesi, significantly increases the flexibility of this transfection system, making it one of the most versatile systems available for Plasmodium.

Aminohydrolases↗
PubMed1986

Isolation of a gene segment expressed by mature schizonts of Plasmodium knowlesi.

Fragments of Plasmodium knowlesi DNA, generated by mung bean nuclease digestion, were ligated into the lambda gt11 vector. This expression library was immunoscreened with a serum which inhibits invasion of erythrocytes by merozoites in vitro and whose primary specificity is directed against a Mr 140 000 merozoite surface antigen. One of the isolated clones contained a 125 base pair insert which hybridized to a 1.8 kilobase species of schizont RNA, indicating that this insert is part of a gene expressed during schizogony.

Animals↗
PubMed1994

Dimorphism and intergenic recombination within the microneme protein (MP-1) gene family of Plasmodium knowlesi.

The microneme protein-1 (MP-1) of Plasmodium knowlesi and Plasmodium vivax facilitates merozoite invasion of the erythrocyte by binding to Duffy blood group antigens. Since this protein is important in the invasion process and is a potential vaccine candidate, it is important to understand the nature of diversity within the MP-1 gene. Nine MP-1 gene sequences were compared from 2 isolates of P. knowlesi and a laboratory strain of P. vivax. The MP-1 genes of P. knowlesi were dimorphic based upon the central hydrophilic regions (III and IV) that were well conserved as alpha and beta types. Other regions were conserved among all P. knowlesi genes except for the amino cysteine-rich region (region II), a region predicted to be the initial contact site of the erythrocyte binding domain. Two distinct sequence motifs and part of a third were identified in region II that had a common identity of 68%. In some MP-1 genes recombination had occurred to create hybrids of the two sequence types. All cysteines and aromatic amino acids of region II were conserved in all genes or within a sequence type. There were 2 apparent recombination points within region II where switching occurred between sequence types. Another possible recombination site, identified as a common sequence motif, was identified in the middle of the hydrophilic region, at the beginning of regions III or IV. Nonsynonymous mutations within region II were biased towards radical amino acid changes, especially towards the carboxyl third, where there were 3 distinct types of sequence. Most synonymous and nonsynonymous nucleotide mutations within regions I, V, and VI were infrequent, individual events and not associated with any particular sequence type. Cysteine-rich regions of the P. vivax MP-1 gene compared to the P. knowlesi genes were characterized by an increased number of synonymous and nonsynonymous changes. This data identifies 2 mechanisms for generation of diversity in the MP-1 gene family, intergenic recombination and nucleotide mutations. Both may be mechanisms the parasite uses to evade the host immune response or to alter erythrocyte receptor specificity.

Amino Acid Sequence↗
PubMed1990

A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium.

The 66-kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian malaria, possesses vaccine-related properties that are thought to originate from a receptor-like role in parasite invasion of erythrocytes. We report the complete sequence of PK66 which allowed the demonstration that highly conserved analogues exist throughout Plasmodium including a recently reported gene from P. falciparum (Peterson, M. G., Marshall, V. M., Smythe, J. A., Crewther, P. E., Lew, A., Silva, A., Anders, R. F., and Kemp, D. J. (1989) Mol. Cell. Biol. 9, 3151-3155). These analogues are highly promising vaccination candidates. The distribution of PK66 changes after schizont rupture in a coordinate manner associated with merozoite invasion. The protein is concentrated at the apical end prior to rupture, following which it can distribute itself entirely across the surface of the free merozoite. During invasion, immunofluorescence studies suggest that, PK66 is excluded from the erythrocyte at, and behind, the invasion interface.

Amino Acid Sequence↗
PubMed1988

Identification of Plasmodium knowlesi erythrocyte binding proteins.

Plasmodium knowlesi, a malaria of Old World monkeys, invades all Duffy blood group positive human erythrocytes and various New World monkey erythrocytes except Cebus apella. We had previously identified a 135 kDa parasite protein in supernatants of P. knowlesi cultures that bound to Duffy positive but not to Duffy negative human erythrocytes [Haynes et al., J. Exp. Med. 167, 1873-1881 (1988)]. We now use New World monkey erythrocytes as a reagent to identify P. knowlesi proteins in culture supernatants that will bind to all New World monkey erythrocytes susceptible to invasion but not to C. apella erythrocytes, which are refractory to invasion. The 135 kDa protein binds to all New World monkey erythrocytes, including C. appella. Another protein of 155 kDa binds to all New World monkey erythrocytes except C. apella. The 155 kDa protein binds to Old World monkey erythrocytes, the natural host of P. knowlesi; it does not bind to human Duffy positive erythrocytes. This and the previous study are the beginning of the identification of parasite proteins of P. knowlesi that bind to erythrocytes in a receptor specific manner.

Animals↗