Network analysis of large phospho-signalling datasets: application to Plasmodium-erythrocyte interactions

Phosphorylation based signalling is a complicated and intertwined series of pathways critical to all domains of life. This interconnectivity, though essential to life, makes understanding and decoding the interactions difficult. Large datasets of phosphorylation interactions through the activity of kinases on their numerous effectors are now being generated, however interpretation of the network environment remains challenging. In humans, many phosphorylation interactions have been identified across published works to form the known phosphorylation interaction network. We overlayed phosphorylation datasets onto this network which provided information to each of the connections. To analyse the datasets now mapped into a network, we designed a pathway analysis that uses random walks to identify chains of phosphorylation events occurring much more or much less frequently than expected. This analysis highlights pathways of phosphorylation that work synergistically, providing a rapid interpretation of the most critical pathways in a given dataset. Here we used datasets of human red blood cells infected with the notable stages of Plasmodium falciparum asexual development. The analysis identified several known signalling interactions, and additional interactions which could form the basis of numerous future studies. The network analysis designed here is widely applicable to any comparative phosphorylation dataset across infection and disease and can provide a rapid and reliable analysis to guide validation studies.

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Fine mapping of Plasmodium falciparum ribosomal phosphoprotein PfP0 revealed sequences with highly specific binding activity to human red blood cells

Journal of Molecular Medicine ◽

10.1007/s00109-009-0533-5 ◽

2009 ◽

Vol 88 (1) ◽

pp. 61-74 ◽

Cited By ~ 3

Author(s):

Gabriela Arevalo-Pinzon ◽

Hernando Curtidor ◽

Claudia Reyes ◽

Martha Pinto ◽

Carolina Vizcaíno ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Fine Mapping ◽

Blood Cells ◽

Specific Binding ◽

Binding Activity ◽

Human Red Blood Cells

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Plasmodium falciparum rhoptry neck protein 5 peptides bind to human red blood cells and inhibit parasite invasion

Peptides ◽

10.1016/j.peptides.2013.07.028 ◽

2014 ◽

Vol 53 ◽

pp. 210-217 ◽

Cited By ~ 5

Author(s):

Hernando Curtidor ◽

Liliana C. Patiño ◽

Gabriela Arévalo-Pinzón ◽

Magnolia Vanegas ◽

Manuel E. Patarroyo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Parasite Invasion ◽

Human Red Blood Cells ◽

Rhoptry Neck Protein

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Identification of Plasmodium falciparum MSP‐1 peptides able to bind to human red blood cells

Parasite Immunology ◽

10.1046/j.1365-3024.1996.d01-15.x ◽

1996 ◽

Vol 18 (10) ◽

pp. 515-526 ◽

Cited By ~ 106

Author(s):

MAURICIO URQUIZA ◽

LUIS E. RODRIGUEZ ◽

JORGE E. SUAREZ ◽

FANNY GUZMÁN ◽

MARISOL OCAMPO ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Human Red Blood Cells

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The effect of mefloquine and volume-regulated anion channel inhibitors on induced transport in Plasmodium falciparum-infected human red blood cells

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2004.01.004 ◽

2004 ◽

Vol 32 (3) ◽

pp. 344-348 ◽

Cited By ~ 7

Author(s):

Henry M Staines ◽

Belinda C Dee ◽

Meng-Ru Shen ◽

J.Clive Ellory

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Anion Channel ◽

Human Red Blood Cells

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Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage

Blood ◽

10.1182/blood.v80.3.801.801 ◽

1992 ◽

Vol 80 (3) ◽

pp. 801-808 ◽

Cited By ~ 88

Author(s):

F Turrini ◽

H Ginsburg ◽

F Bussolino ◽

GP Pescarmona ◽

MV Serra ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Blood Cell ◽

Developmental Stage ◽

Red Blood Cell ◽

Immunoglobulin G ◽

Blood Cells ◽

Protein A ◽

Human Monocytes ◽

Human Red Blood Cells ◽

Igg Binding

Abstract The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring- forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG-, and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement- dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis.

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Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions

Blood ◽

10.1182/blood.v78.3.812.812 ◽

1991 ◽

Vol 78 (3) ◽

pp. 812-819 ◽

Cited By ~ 119

Author(s):

DK Kaul ◽

EF Jr Roth ◽

RL Nagel ◽

RJ Howard ◽

SM Handunnetti

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Peripheral Resistance ◽

Inverse Correlation ◽

Rosette Formation ◽

Flow Conditions ◽

Human Red Blood Cells ◽

Venular Endothelium

Abstract The occurrence of rosetting of Plasmodium falciparum-infected human red blood cells (IRBC) with uninfected red blood cells (RBC) and its potential pathophysiologic consequences were investigated under flow conditions using the perfused rat mesocecum vasculature. Perfusion experiments were performed using two knobby (K+) lines of P falciparum, ie, rosetting positive (K+R+) and rosetting negative (K+R-). The infusion of K+R+ IRBC resulted in higher peripheral resistance (PRU) than K+R- IRBC (P less than .0012). Video microscopy showed that under conditions of flow, in addition to cytoadherence of K+R+ IRBC to the venular endothelium, rosette formation was also restricted to venules, especially in the areas of slow flow. Rosettes were absent in arterioles and were presumably dissociated by higher wall shear rates. The presence of rosettes in the venules must therefore reflect their rapid reformation after disruption. Cytoadherence of K+R+ IRBC was characterized by formation of focal clusters along the venular wall. In addition, large aggregates of RBC were frequently observed at venular junctions, probably as a result of interaction between flowing rosettes, free IRBC, and uninfected RBC. In contrast, the infusion of K+R+ IRBC resulted in diffuse cytoadherence of these cells exclusively to the venular endothelium but not in rosetting or large aggregate formation. The cytoadherence of K+R+ IRBC showed strong inverse correlation with the venular diameter (r = -.856, P less than .00001). Incubation of K+R+ IRBC with heparin and with monoclonal antibodies to glycoprotein IV/CD36 abolished the rosette formation and resulted in decreased PRU and microvascular blockage. These findings demonstrate that rosetting of K+R+ IRBC with uninfected RBC enhances vasocclusion, suggesting an important in vivo role for rosetting in the microvascular sequestration of P falciparum-infected RBC.

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Distribution of Duffy Phenotypes among Plasmodium vivax Infections in Sudan

Genes ◽

10.3390/genes10060437 ◽

2019 ◽

Vol 10 (6) ◽

pp. 437

Author(s):

Musab M.A. Albsheer ◽

Kareen Pestana ◽

Safaa Ahmed ◽

Mohammed Elfaki ◽

Eiman Gamil ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Vivax ◽

Real Time Pcr ◽

Blood Cells ◽

Vivax Infection ◽

Quantitative Real Time Pcr ◽

East African ◽

African Countries ◽

Human Red Blood Cells ◽

Duffy Negative

Negative Duffy expression on the surface of human red blood cells was believed to be a barrier for Plasmodium vivax infection in most Africans. However, P. vivax has been demonstrated to infect Duffy-negative individuals in several Central and East African countries. In this study, we investigated the distribution of Duffy blood group phenotypes with regard to P. vivax infection and parasitemia in Sudan. Out of 992 microscopic-positive malaria samples, 190 were identified as P. vivax positive infections. Among them, 186 were P. vivax mono-infections and 4 were mixed P. vivax and Plasmodium falciparum infections. A subset of 77 samples was estimated with parasitemia by quantitative real-time PCR. Duffy codons were sequenced from the 190 P. vivax positive samples. We found that the Duffy Fy(a-b+) phenotype was the most prevalent, accounting for 67.9% of all P. vivax infections, while homozygous Duffy-negative Fy(a-b-) accounted for 17.9% of the P. vivax infections. The prevalence of infection in Fy(a-b+) and Fy(a+b-)were significantly higher than Fy(a-b-) phenotypes (p = 0.01 and p < 0.01, respectively). A significantly low proportion of P. vivax infection was observed in Duffy negative individuals Fy(a-b-). This study highlights the prevalence of P. vivax in Duffy-negatives in Sudan and indicates low parasitemia among the Duffy-negative individuals.

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