Babesia divergens and Plasmodium falciparum Use Common Receptors, Glycophorins A and B, To Invade the Human Red Blood Cell

ABSTRACT Babesiosis has long been recognized as an economically important disease of cattle, but only in the last 30 years has Babesia been recognized as an important pathogen in humans. Invasion of erythrocytes is an integral part of the Babesia life cycle. However, very little information is available on the molecules involved in this process, in contrast to another hemoparasite, Plasmodium falciparum. Using invasion assays into normal red blood cells (RBCs), enzyme-treated cells, and clinically mutant cells, we showed that Babesia divergens uses neuraminidase- and trypsin-sensitive receptors to enter the RBCs, of which glycophorins A and B are the prominent ones. These results could have broad implications relating to evolutionarily conserved mechanisms of host cell entry in these related Apicomplexan parasites and pave the way toward a detailed molecular analysis of erythrocyte invasion in B. divergens.

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Plasmodium falciparum Field Isolates Commonly Use Erythrocyte Invasion Pathways That Are Independent of Sialic Acid Residues of Glycophorin A

Infection and Immunity ◽

10.1128/iai.67.11.5784-5791.1999 ◽

1999 ◽

Vol 67 (11) ◽

pp. 5784-5791 ◽

Cited By ~ 116

Author(s):

Jude Nnaemeka Okoyeh ◽

C. R. Pillai ◽

Chetan E. Chitnis

Keyword(s):

Plasmodium Falciparum ◽

Sialic Acid ◽

Vaccine Development ◽

Glycophorin A ◽

Invasion Pathways ◽

Field Isolates ◽

Erythrocyte Invasion ◽

In Vitro Invasion ◽

Invasion Assays

ABSTRACT Erythrocyte invasion by malaria parasites is mediated by specific molecular interactions. Sialic acid residues of glycophorin A are used as invasion receptors by Plasmodium falciparum. In vitro invasion studies have demonstrated that some cloned P. falciparum lines can use alternate receptors independent of sialic acid residues of glycophorin A. It is not known if invasion by alternate pathways occurs commonly in the field. In this study, we used in vitro growth assays and erythrocyte invasion assays to determine the invasion phenotypes of 15 P. falciparum field isolates. Of the 15 field isolates tested, 5 multiply in both neuraminidase and trypsin-treated erythrocytes, 3 multiply in neuraminidase-treated but not trypsin-treated erythrocytes, and 4 multiply in trypsin-treated but not neuraminidase-treated erythrocytes; 12 of the 15 field isolates tested use alternate invasion pathways that are not dependent on sialic acid residues of glycophorin A. Alternate invasion pathways are thus commonly used by P. falciparum field isolates. Typing based on two polymorphic markers, MSP-1 and MSP-2, and two microsatellite markers suggests that only 1 of the 15 field isolates tested contains multiple parasite genotypes. Individual P. falciparum lines can thus use multiple invasion pathways in the field. These observations have important implications for malaria vaccine development efforts based on EBA-175, the P. falciparumprotein that binds sialic acid residues of glycophorin A during invasion. It may be necessary to target parasite ligands responsible for the alternate invasion pathways in addition to EBA-175 to effectively block erythrocyte invasion by P. falciparum.

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Use of magnetically purified Plasmodium falciparum parasites improves the accuracy of erythrocyte invasion assays

Experimental Parasitology ◽

10.1016/j.exppara.2010.05.007 ◽

2010 ◽

Vol 126 (2) ◽

pp. 278-280 ◽

Cited By ~ 7

Author(s):

Adam H. Bates ◽

Jianbing Mu ◽

Hongying Jiang ◽

Rick M. Fairhurst ◽

Xin-zhuan Su

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Invasion ◽

Invasion Assays

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Faculty Opinions recommendation of Host cell entry by apicomplexa parasites requires actin polymerization in the host cell.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1157765.618988 ◽

2009 ◽

Author(s):

Marc Lecuit ◽

Serge Mostowy

Keyword(s):

Host Cell ◽

Actin Polymerization ◽

Cell Entry ◽

Host Cell Entry

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Faculty Opinions recommendation of Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718453306.793496526 ◽

2014 ◽

Author(s):

Vernon Carruthers

Keyword(s):

Host Cell ◽

Cell Entry ◽

Host Cell Entry

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Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

Scientific Reports ◽

10.1038/s41598-021-83513-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Malabika Chakrabarti ◽

Nishant Joshi ◽

Geeta Kumari ◽

Preeti Singh ◽

Rumaisha Shoaib ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Life Cycle ◽

Specific Protein ◽

Parasite Growth ◽

Growth And Survival ◽

Apicomplexan Parasites ◽

Parasite Replication ◽

Main Components ◽

Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

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Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens

PLoS Pathogens ◽

10.1371/journal.ppat.1002991 ◽

2012 ◽

Vol 8 (11) ◽

pp. e1002991 ◽

Cited By ~ 84

Author(s):

Andrew R. Williams ◽

Alexander D. Douglas ◽

Kazutoyo Miura ◽

Joseph J. Illingworth ◽

Prateek Choudhary ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Invasion ◽

Merozoite Antigens

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Functional Characterization of a Redundant Plasmodium TRAP Family Invasin, TRAP-Like Protein, by Aldolase Binding and a Genetic Complementation Test

Eukaryotic Cell ◽

10.1128/ec.00089-08 ◽

2008 ◽

Vol 7 (6) ◽

pp. 1062-1070 ◽

Cited By ~ 39

Author(s):

Kirsten Heiss ◽

Hui Nie ◽

Sumit Kumar ◽

Thomas M. Daly ◽

Lawrence W. Bergman ◽

...

Keyword(s):

Functional Characterization ◽

Cell Entry ◽

Host Cells ◽

Complementation Test ◽

Type I ◽

Cycle Progression ◽

Targeted Gene Disruption ◽

Specific Host ◽

Host Cell Entry

ABSTRACT Efficient and specific host cell entry is of exquisite importance for intracellular pathogens. Parasites of the phylum Apicomplexa are highly motile and actively enter host cells. These functions are mediated by type I transmembrane invasins of the TRAP family that link an extracellular recognition event to the parasite actin-myosin motor machinery. We systematically tested potential parasite invasins for binding to the actin bridging molecule aldolase and complementation of the vital cytoplasmic domain of the sporozoite invasin TRAP. We show that the ookinete invasin CTRP and a novel, structurally related protein, termed TRAP-like protein (TLP), are functional members of the TRAP family. Although TLP is expressed in invasive stages, targeted gene disruption revealed a nonvital role during life cycle progression. This is the first genetic analysis of TLP, encoding a redundant TRAP family invasin, in the malaria parasite.

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Distinct Th1- and Th2-Type Prenatal Cytokine Responses to Plasmodium falciparum Erythrocyte Invasion Ligands

Infection and Immunity ◽

10.1128/iai.73.6.3462-3470.2005 ◽

2005 ◽

Vol 73 (6) ◽

pp. 3462-3470 ◽

Cited By ~ 70

Author(s):

Indu Malhotra ◽

Peter Mungai ◽

Eric Muchiri ◽

John Ouma ◽

Shobhona Sharma ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Cord Blood ◽

Interleukin 2 ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Cd8 Cells ◽

Erythrocyte Invasion ◽

Cytokine Responses ◽

Th1 And Th2 Responses ◽

Th1 And Th2

ABSTRACT Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.

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Plasmodium falciparum Line-Dependent Association ofIn VitroGrowth-Inhibitory Activity and Risk of Malaria

Infection and Immunity ◽

10.1128/iai.06190-11 ◽

2012 ◽

Vol 80 (5) ◽

pp. 1900-1908 ◽

Cited By ~ 11

Author(s):

Josea Rono ◽

Anna Färnert ◽

Daniel Olsson ◽

Faith Osier ◽

Ingegerd Rooth ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Inhibitory Activity ◽

Content Type ◽

Phenotypic Differences ◽

Erythrocyte Invasion ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

Control Study

ABSTRACTPlasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA)in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using threeP. falciparumlines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96;P= 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on theP. falciparumline and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence ofP. falciparumerythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.

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