<i>Plasmodium knowlesi</i> in the marmoset (<i>Callithrix jacchus</i>)

Langhorne, Jean; Cohen, S.

doi:10.1017/s0031182000048599

Cited by 15 publications

(14 citation statements)

References 14 publications

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“…4 ). Thus, it is likely that P. knowlesi is capable of invading its macaque host red blood cells via a DARC-independent pathway, confirming previous observations 21 22 23 24 .…”

Section: Discussionsupporting

confidence: 87%

Invasion characteristics of a Plasmodium knowlesi line newly isolated from a human

Amir

Russell

Liew

et al. 2016

Sci Rep

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Plasmodium knowlesi is extensively used as an important malaria model and is now recognized as an important cause of human malaria in Malaysia. The strains of P. knowlesi currently used for research were isolated many decades ago, raising concerns that they might no longer be representative of contemporary parasite populations. We derived a new P. knowlesi line (University Malaya line, UM01), from a patient admitted in Kuala Lumpur, Malaysia, and compared it with a human-adapted laboratory line (A1-H.1) derived from the P. knowlesi H strain. The UM01 and A1-H.1 lines readily invade human and macaque (Macaca fascicularis) normocytes with a preference for reticulocytes. Whereas invasion of human red blood cells was dependent on the presence of the Duffy antigen/receptor for chemokines (DARC) for both parasite lines, this was not the case for macaque red blood cells. Nonetheless, differences in invasion efficiency, gametocyte production and the length of the asexual cycle were noted between the two lines. It would be judicious to isolate and characterise numerous P. knowlesi lines for use in future experimental investigations of this zoonotic species.

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“…4 ). Thus, it is likely that P. knowlesi is capable of invading its macaque host red blood cells via a DARC-independent pathway, confirming previous observations 21 22 23 24 .…”

Section: Discussionsupporting

confidence: 87%

Invasion characteristics of a Plasmodium knowlesi line newly isolated from a human

Amir

Russell

Liew

et al. 2016

Sci Rep

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“…P. knowlesi is a zoonotic pathogen that is permissive in a variety of differentially susceptible non-human primates [48], [49], [50], [51], [52]. Surely there is a compelling argument to use P. knowlesi as a robust representative animal model for malaria pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Disease Progression in Plasmodium knowlesi Malaria Is Linked to Variation in Invasion Gene Family Members

et al. 2014

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Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥0.34 p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region.

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“…Gibbons are neither natural nor normally experimental hosts for P. knowlesi , but can be infected with this parasite. Although New World monkeys, squirrel, owl and marmoset monkeys are known to be very susceptible to P. knowlesi infection [42-44], erythrocytes from these species did not form rosettes with PkNBPXb-II. Similarly, and importantly, human erythrocytes did not bind PkNBPXb-II or native NBPXb, even though P. knowlesi does infect humans.…”

Section: Discussionmentioning

confidence: 99%

Two functional reticulocyte binding-like (RBL) invasion ligands of zoonotic Plasmodium knowlesi exhibit differential adhesion to monkey and human erythrocytes

Semenya

Tran

Meyer

et al. 2012

Malar J

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BackgroundPlasmodium knowlesi is a monkey malaria species that is becoming a serious public health concern infecting hundreds and perhaps thousands of humans in Southeast Asia. Invasion of erythrocytes by merozoites entails a cascade of molecular interactions. One step involves the adhesion of Plasmodium reticulocyte binding-like (RBL) proteins. Plasmodium knowlesi merozoites express only two RBL invasion ligands, known as Normocyte Binding Proteins (PkNBPXa and PkNBPXb).MethodsOverlapping N-terminal regions of PkNBPXa and PkNBPXb were expressed in COS7 cells and tested for surface expression and adhesion to rhesus monkey erythrocytes. Subsequent tests to study specific receptor ligand interactions included adhesion to a panel of human and non-human primate erythrocytes, enzymatic treatment, and site directed mutagenesis.ResultsAn N-terminal cysteine-rich region of PkNBPXb (PkNBPXb-II) exhibited specific adhesion to rhesus monkey erythrocytes. Mutation of four of five cysteines in PkNBPXb-II interfered with its surface expression on COS7 cells, suggesting disulphide bond conformation is critical for intracellular trafficking. Binding of PkNBPXb-II was abolished when rhesus erythrocytes were pre-treated with chymotrypsin, but not trypsin or neuraminidase. PkNBPXb-II also bound other Old World monkey species and gibbon erythrocytes. However, erythrocytes from other primate species including humans did not bind to PkNBPXb-II or native PkNBPXb. Importantly, unlike PkNBPXb, PkNBPXa bound human erythrocytes, and this binding was independent of the Duffy blood group determinant.ConclusionsThe data reported here begins to clarify the functional domains of the P. knowlesi RBLs. A binding domain has been identified and characterized in PkNBPXb. Notably, this study demonstrates that unlike PkNBPXb, PkNBPXa can bind to human erythrocytes, suggesting that PkNBPXa may function as a ligand to enable the invasion of P. knowlesi merozoites into human cells.

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Plasmodium knowlesi in the marmoset (Callithrix jacchus)

Cited by 15 publications

References 14 publications

Invasion characteristics of a Plasmodium knowlesi line newly isolated from a human

Invasion characteristics of a Plasmodium knowlesi line newly isolated from a human

Disease Progression in Plasmodium knowlesi Malaria Is Linked to Variation in Invasion Gene Family Members

Two functional reticulocyte binding-like (RBL) invasion ligands of zoonotic Plasmodium knowlesi exhibit differential adhesion to monkey and human erythrocytes

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