scholarly journals The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion

2020 ◽  
Author(s):  
Christine R Collins ◽  
Fiona Hackett ◽  
Steven A Howell ◽  
Ambrosius P Snijders ◽  
Matthew RG Russell ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Parasitophorous Vacuole ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
List Type ◽  
Rbc Membrane ◽  
Membrane Sealing

AbstractRed blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either abortive invasion with rapid RBC lysis, or successful entry but developmental arrest. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for host RBC membrane sealing following parasite internalisation and for correct functioning of merozoite surface proteins.Key highlightsMany malaria parasite surface proteins are shed by SUB2 during RBC invasionSUB2-null merozoites either induce rapid host RBC lysis, or invade then dieMerozoite surface protein shedding is crucial for host RBC membrane sealing

scholarly journals The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Christine R Collins ◽  
Fiona Hackett ◽  
Steven A Howell ◽  
Ambrosius P Snijders ◽  
Matthew RG Russell ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Parasitophorous Vacuole ◽  
Surface Proteins ◽  
Intracellular Replication ◽  
Vacuole Membrane ◽  
Developmental Arrest ◽  
Rbc Membrane ◽  
Membrane Bound ◽  
Membrane Sealing

Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either abortive invasion with rapid RBC lysis, or successful entry but developmental arrest. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for host RBC membrane sealing following parasite internalisation and for correct functioning of merozoite surface proteins.

scholarly journals Antimalarial Activity of Cupredoxins

2013 ◽  
Vol 288 (29) ◽  
pp. 20896-20907 ◽  
Author(s):  
Isabel Cruz-Gallardo ◽  
Irene Díaz-Moreno ◽  
Antonio Díaz-Quintana ◽  
Antonio Donaire ◽  
Adrián Velázquez-Campoy ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Antimalarial Activity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Food Vacuole ◽  
Parasite Growth ◽  
Titration Calorimetry ◽  
Erythrocyte Invasion ◽  
Promising Target

The discovery of effective new antimalarial agents is urgently needed. One of the most frequently studied molecules anchored to the parasite surface is the merozoite surface protein-1 (MSP1). At red blood cell invasion MSP1 is proteolytically processed, and the 19-kDa C-terminal fragment (MSP119) remains on the surface and is taken into the red blood cell, where it is transferred to the food vacuole and persists until the end of the intracellular cycle. Because a number of specific antibodies inhibit erythrocyte invasion and parasite growth, MSP119 is therefore a promising target against malaria. Given the structural homology of cupredoxins with the Fab domain of monoclonal antibodies, an approach combining NMR and isothermal titration calorimetry (ITC) measurements with docking calculations based on BiGGER is employed on MSP119-cupredoxin complexes. Among the cupredoxins tested, rusticyanin forms a well defined complex with MSP119 at a site that overlaps with the surface recognized by the inhibitory antibodies. The addition of holo-rusticyanin to infected cells results in parasitemia inhibition, but negligible effects on parasite growth can be observed for apo-rusticyanin and other proteins of the cupredoxin family. These findings point to rusticyanin as an excellent therapeutic tool for malaria treatment and provide valuable information for drug design.

scholarly journals Author response: The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion

2020 ◽  
Author(s):  
Christine R Collins ◽  
Fiona Hackett ◽  
Steven A Howell ◽  
Ambrosius P Snijders ◽  
Matthew RG Russell ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Author Response ◽  
Red Blood Cell Membrane ◽  
Membrane Sealing

Extensive proteolytic processing of the malaria parasite merozoite surface protein 7 during biosynthesis and parasite release from erythrocytes

2007 ◽  
Vol 151 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Justin A. Pachebat ◽  
Madhusudan Kadekoppala ◽  
Munira Grainger ◽  
Anton R. Dluzewski ◽  
Ruwani S. Gunaratne ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Proteolytic Processing

scholarly journals Altered Levels of Desaturation and ω-6 Fatty Acids in Breast Cancer Patients’ Red Blood Cell Membranes

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 469
Author(s):  
Javier Amézaga ◽  
Gurutze Ugartemendia ◽  
Aitziber Larraioz ◽  
Nerea Bretaña ◽  
Aizpea Iruretagoyena ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Blood Cell ◽  
Cancer Patients ◽  
Red Blood Cell ◽  
Breast Cancer Patients ◽  
Disease Evolution ◽  
Lipidomic Analysis ◽  
Rbc Membrane

Red blood cell (RBC) membrane can reflect fatty acid (FA) contribution from diet and biosynthesis. In cancer, membrane FAs are involved in tumorigenesis and invasiveness, and are indicated as biomarkers to monitor the disease evolution as well as potential targets for therapies and nutritional strategies. The present study provides RBC membrane FA profiles in recently diagnosed breast cancer patients before starting chemotherapy treatment. Patients and controls were recruited, and their dietary habits were collected. FA lipidomic analysis of mature erythrocyte membrane phospholipids in blood samples was performed. Data were adjusted to correct for the effects of diet, body mass index (BMI), and age, revealing that patients showed lower levels of saturated fatty acids (SFA) and higher levels of monounsaturated fatty acid, cis-vaccenic (25%) than controls, with consequent differences in desaturase enzymatic index (∆9 desaturase, –13.1%). In the case of polyunsaturated fatty acids (PUFA), patients had higher values of ω-6 FA (C18:2 (+11.1%); C20:4 (+7.4%)). RBC membrane lipidomic analysis in breast cancer revealed that ω-6 pathways are favored. These results suggest new potential targets for treatments and better nutritional guidelines.

Red blood cell (RBC) age at collection and storage influences RBC membrane-associated carbohydrates and lectin binding

Transfusion ◽  
2007 ◽  
Vol 47 (6) ◽  
pp. 966-968 ◽  
Author(s):  
Rosemary L. Sparrow ◽  
Margaret F. Veale ◽  
Geraldine Healey ◽  
Katherine A. Payne
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Lectin Binding ◽  
Rbc Membrane ◽  
And Storage

scholarly journals Oral Immunization with a Combination of Plasmodium yoelii Merozoite Surface Proteins 1 and 4/5 Enhances Protection against Lethal Malaria Challenge

2004 ◽  
Vol 72 (10) ◽  
pp. 6172-6175 ◽  
Author(s):  
Lina Wang ◽  
Matthew W. Goschnick ◽  
Ross L. Coppel
Keyword(s):  
Escherichia Coli ◽  
Malaria Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Oral Immunization ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Merozoite Surface Protein 1

ABSTRACT Oral immunization of mice with Escherichia coli-expressed Plasmodium yoelii merozoite surface protein 4/5 or the C-terminal 19-kDa fragment of merozoite surface protein 1 induced systemic antibody responses and protected mice against lethal malaria infection. A combination of these two proteins administered orally conferred improved protection compared to that conferred by either protein administered alone.

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