The cellular and molecular basis for malaria parasite invasion of the human red blood cell

Malaria is a major disease of humans caused by protozoan parasites from the genus Plasmodium. It has a complex life cycle; however, asexual parasite infection within the blood stream is responsible for all disease pathology. This stage is initiated when merozoites, the free invasive blood-stage form, invade circulating erythrocytes. Although invasion is rapid, it is the only time of the life cycle when the parasite is directly exposed to the host immune system. Significant effort has, therefore, focused on identifying the proteins involved and understanding the underlying mechanisms behind merozoite invasion into the protected niche inside the human erythrocyte.

[1]  Geoffrey I. McFadden,et al.  Plastid in human parasites , 1996, Nature.

[2]  A. Holder,et al.  Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein , 1994, The Journal of experimental medicine.

[3]  J. Baum,et al.  Cytoskeletal and membrane remodelling during malaria parasite invasion of the human erythrocyte , 2011, British journal of haematology.

[4]  Jonathan E. Allen,et al.  Genome sequence of the human malaria parasite Plasmodium falciparum , 2002, Nature.

[5]  L. Miller,et al.  Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease , 2007, Proceedings of the National Academy of Sciences.

[6]  Rogerio Amino,et al.  Manipulation of Host Hepatocytes by the Malaria Parasite for Delivery into Liver Sinusoids , 2006, Science.

[7]  C. Janse,et al.  PTRAMP; a conserved Plasmodium thrombospondin-related apical merozoite protein. , 2004, Molecular and biochemical parasitology.

[8]  P. Alzari,et al.  Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1-42 maturase. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Triglia,et al.  Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species , 2000, Molecular Microbiology.

[10]  Christopher J. Tonkin,et al.  Spatial Localisation of Actin Filaments across Developmental Stages of the Malaria Parasite , 2012, PloS one.

[11]  J. Rayner,et al.  Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes , 2003, The EMBO journal.

[12]  J. Dalton,et al.  Receptor-like specificity of a Plasmodium knowlesi malarial protein that binds to Duffy antigen ligands on erythrocytes , 1988, The Journal of experimental medicine.

[13]  Christopher J. Tonkin,et al.  A Novel Family of Apicomplexan Glideosome-associated Proteins with an Inner Membrane-anchoring Role , 2009, The Journal of Biological Chemistry.

[14]  L. Miller,et al.  Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite , 1978, The Journal of cell biology.

[15]  Virander S. Chauhan,et al.  A novel Plasmodium falciparum erythrocyte binding protein associated with the merozoite surface, PfDBLMSP. , 2009, International journal for parasitology.

[16]  J. Dubremetz,et al.  The moving junction of apicomplexan parasites: a key structure for invasion , 2011, Cellular microbiology.

[17]  S. Krishna,et al.  A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. , 2000, Parasitology today.

[18]  Siarhei Maslau,et al.  Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Adams,et al.  A family of erythrocyte binding proteins of malaria parasites. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Gilberger,et al.  Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions. , 2011, Nature communications.

[21]  J. Stockman A Field Trial to Assess a Blood-Stage Malaria Vaccine , 2013 .

[22]  A. Cowman,et al.  Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species , 2000, Nature Medicine.

[23]  Dave Richard,et al.  Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand , 2010, Proceedings of the National Academy of Sciences.

[24]  P. Baldacci,et al.  Independent roles of apical membrane antigen 1 and rhoptry neck proteins during host cell invasion by apicomplexa. , 2011, Cell host & microbe.

[25]  C. Chitnis,et al.  Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. , 1994, Science.

[26]  Xavier Ambroggio,et al.  Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion , 2011, Proceedings of the National Academy of Sciences.

[27]  T. Gilberger,et al.  A Conserved Region in the EBL Proteins Is Implicated in Microneme Targeting of the Malaria Parasite Plasmodium falciparum* , 2006, Journal of Biological Chemistry.

[28]  G. Butcher,et al.  Properties of Protective Malarial Antibody , 1970, Nature.

[29]  J. Haynes,et al.  Primary structure of the 175K Plasmodium falciparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion , 1990, The Journal of cell biology.

[30]  P. Gerold,et al.  Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum. , 1996, Molecular and biochemical parasitology.

[31]  L. Aravind,et al.  Structure of the Plasmodium 6-cysteine s48/45 domain , 2012, Proceedings of the National Academy of Sciences.

[32]  A. Thomas,et al.  The RON2-AMA1 Interaction is a Critical Step in Moving Junction-Dependent Invasion by Apicomplexan Parasites , 2011, PLoS pathogens.

[33]  H. Bujard,et al.  The Merozoite Surface Protein 1 Complex of Human Malaria Parasite Plasmodium falciparum , 2003, Journal of Biological Chemistry.

[34]  K. Deitsch,et al.  Antigenic variation and the generation of diversity in malaria parasites. , 2012, Current opinion in microbiology.

[35]  T. Prentice World Health Report , 2013 .

[36]  J. Zimmerberg,et al.  Membrane Transformation during Malaria Parasite Release from Human Red Blood Cells , 2005, Current Biology.

[37]  T. Triglia,et al.  Characterisation of two novel proteins from the asexual stage of Plasmodium falciparum, H101 and H103. , 2005, Molecular and biochemical parasitology.

[38]  C. Chitnis,et al.  Distinct External Signals Trigger Sequential Release of Apical Organelles during Erythrocyte Invasion by Malaria Parasites , 2010, PLoS pathogens.

[39]  S. Cohen,et al.  The primary structure of epidermal growth factor. , 1972, The Journal of biological chemistry.

[40]  M. Wahlgren,et al.  Human antibodies to a Mr 155,000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Y. Chinzei,et al.  Two proteins with 6‐cys motifs are required for malarial parasites to commit to infection of the hepatocyte , 2005, Molecular microbiology.

[42]  A. Tartar,et al.  Merozoite surface protein-3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes. , 1994, Blood.

[43]  P. Gilson,et al.  Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum merozoites. , 2009, International journal for parasitology.

[44]  Caroline W. Kabaria,et al.  The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009 , 2010, PLoS neglected tropical diseases.

[45]  M. Mota,et al.  A toolbox to study liver stage malaria. , 2011, Trends in parasitology.

[46]  S. Ralph,et al.  Interaction between Plasmodium falciparum Apical Membrane Antigen 1 and the Rhoptry Neck Protein Complex Defines a Key Step in the Erythrocyte Invasion Process of Malaria Parasites , 2010, The Journal of Biological Chemistry.

[47]  J. Boothroyd,et al.  Identification of the Moving Junction Complex of Toxoplasma gondii: A Collaboration between Distinct Secretory Organelles , 2005, PLoS pathogens.

[48]  S. Ralph,et al.  Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. , 2009, International journal for parasitology.

[49]  R. Ménard,et al.  Host cell entry by apicomplexa parasites requires actin polymerization in the host cell. , 2009, Cell host & microbe.

[50]  T. Speed,et al.  Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins inPlasmodium vivax , 2001, Infection and Immunity.

[51]  M. Abkarian,et al.  A novel mechanism for egress of malarial parasites from red blood cells. , 2011, Blood.

[52]  D. Soldati,et al.  ‘The glideosome’: a dynamic complex powering gliding motion and host cell invasion by Toxoplasma gondii , 2002, Molecular microbiology.

[53]  K. Miura,et al.  Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process , 2009, PLoS pathogens.

[54]  W. Whitehouse,et al.  Invasion of erythrocytes by malaria merozoites. , 1975, Science.

[55]  N. Van Rooijen,et al.  Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes. , 2006, Blood.

[56]  A. Cowman,et al.  Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. , 2008, The Journal of clinical investigation.

[57]  Christopher G. Adda,et al.  Merozoite surface protein 2 of Plasmodium falciparum: expression, structure, dynamics, and fibril formation of the conserved N-terminal domain. , 2007, Biopolymers.

[58]  S. Hay,et al.  The global distribution of clinical episodes of Plasmodium falciparum malaria , 2005, Nature.

[59]  I. Coppens,et al.  A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites. , 2004, Molecular and biochemical parasitology.

[60]  S. Krishna,et al.  Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic schizonts , 2000, Parasitology.

[61]  Malcolm J. McConville,et al.  Distinct Protein Classes Including Novel Merozoite Surface Antigens in Raft-like Membranes of Plasmodium falciparum* , 2005, Journal of Biological Chemistry.

[62]  J. Dubremetz,et al.  Export of a Toxoplasma gondii Rhoptry Neck Protein Complex at the Host Cell Membrane to Form the Moving Junction during Invasion , 2009, PLoS pathogens.

[63]  A. Cowman,et al.  Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes. , 2012, Vaccine.

[64]  J. Haynes,et al.  A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac(alpha 2- 3)Gal- sequences of glycophorin A , 1992, The Journal of cell biology.

[65]  T. Mitamura,et al.  Serine Repeat Antigen (SERA5) Is Predominantly Expressed among the SERA Multigene Family of Plasmodium falciparum, and the Acquired Antibody Titers Correlate with Serum Inhibition of the Parasite Growth* , 2002, The Journal of Biological Chemistry.

[66]  A. Holder The precursor to major merozoite surface antigens: structure and role in immunity. , 1988, Progress in allergy.

[67]  X. Ambroggio,et al.  Analysis of the Conformation and Function of the Plasmodium falciparum Merozoite Proteins MTRAP and PTRAMP , 2012, Eukaryotic Cell.

[68]  T. Speed,et al.  Evidence for a Common Role for the Serine-Type Plasmodium falciparum Serine Repeat Antigen Proteases: Implications for Vaccine and Drug Design , 2007, Infection and Immunity.

[69]  A. Thomas,et al.  Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. , 1994, Molecular and biochemical parasitology.

[70]  Danny W. Wilson,et al.  Reticulocyte and Erythrocyte Binding-Like Proteins Function Cooperatively in Invasion of Human Erythrocytes by Malaria Parasites , 2010, Infection and Immunity.

[71]  A. Cowman,et al.  Erythrocyte and reticulocyte binding-like proteins of Plasmodium falciparum. , 2012, Trends in parasitology.

[72]  Deepak Gaur,et al.  Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion. , 2008, Cell host & microbe.

[73]  Michael J. Blackman,et al.  Global Identification of Multiple Substrates for Plasmodium falciparum SUB1, an Essential Malarial Processing Protease , 2011, Infection and Immunity.

[74]  Dave Richard,et al.  Super resolution dissection of coordinated events behind malaria parasite invasion of the human erythrocyte , 2014 .

[75]  S. Howell,et al.  Systematic Genetic Analysis of the Plasmodium falciparum MSP7-Like Family Reveals Differences in Protein Expression, Location, and Importance in Asexual Growth of the Blood-Stage Parasite , 2010, Eukaryotic Cell.

[76]  S. Ralph,et al.  Independent Translocation of Two Micronemal Proteins in Developing Plasmodium falciparum Merozoites , 2002, Infection and Immunity.

[77]  Ogobara K. Doumbo,et al.  The pathogenic basis of malaria , 2002, Nature.

[78]  Alexander G. Maier,et al.  Molecular Mechanism for Switching of P. falciparum Invasion Pathways into Human Erythrocytes , 2005, Science.

[79]  T. Speed,et al.  Enzymic, Phylogenetic, and Structural Characterization of the Unusual Papain-like Protease Domain of Plasmodium falciparum SERA5* , 2003, Journal of Biological Chemistry.

[80]  C. Withers-Martinez,et al.  Subcellular Discharge of a Serine Protease Mediates Release of Invasive Malaria Parasites from Host Erythrocytes , 2007, Cell.

[81]  A. Cowman,et al.  Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations , 2003, Nature Medicine.

[82]  D. Ménard,et al.  Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people , 2010, Proceedings of the National Academy of Sciences.

[83]  L. Bannister,et al.  Structure and development of the surface coat of erythrocytic merozoites of Plasmodium knowlesi , 2004, Cell and Tissue Research.

[84]  Steven S. Oh,et al.  Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[85]  Juraj Kabat,et al.  Glycophorin B is the erythrocyte receptor of Plasmodium falciparum erythrocyte-binding ligand, EBL-1 , 2009, Proceedings of the National Academy of Sciences.

[86]  Christopher G. Adda,et al.  Recombinant protein vaccines against the asexual blood-stages of Plasmodium falciparum , 2010, Human vaccines.

[87]  H. Bujard,et al.  Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth , 2010, Molecular microbiology.

[88]  C. G. Black,et al.  Identification of Rhoptry Trafficking Determinants and Evidence for a Novel Sorting Mechanism in the Malaria Parasite Plasmodium falciparum , 2009, PLoS pathogens.

[89]  Ute Woehlbier,et al.  Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum* , 2006, Journal of Biological Chemistry.

[90]  S. Ralph,et al.  An EGF-like Protein Forms a Complex with PfRh5 and Is Required for Invasion of Human Erythrocytes by Plasmodium falciparum , 2011, PLoS pathogens.

[91]  A. Cowman,et al.  Invasion of Red Blood Cells by Malaria Parasites , 2006, Cell.

[92]  A. Cowman,et al.  Lack of Evidence from Studies of Soluble Protein Fragments that Knops Blood Group Polymorphisms in Complement Receptor-Type 1 Are Driven by Malaria , 2012, PloS one.

[93]  D. Roos,et al.  Origin, targeting, and function of the apicomplexan plastid. , 1999, Current opinion in microbiology.

[94]  X. Su,et al.  Complex polymorphisms in an approximately 330 kDa protein are linked to chloroquine-resistant P. falciparum in Southeast Asia and Africa. , 1997, Cell.

[95]  L. Sibley,et al.  Cytoskeleton of Apicomplexan Parasites , 2002, Microbiology and Molecular Biology Reviews.

[96]  T. Gilberger,et al.  Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite , 2010, PLoS pathogens.

[97]  X. Su,et al.  Complex Polymorphisms in an ∼330 kDa Protein Are Linked to Chloroquine-Resistant P. falciparum in Southeast Asia and Africa , 1997, Cell.

[98]  Dominic P. Kwiatkowski,et al.  BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum , 2011, Nature.

[99]  J. Boothroyd,et al.  Plasmodium falciparum AMA1 Binds a Rhoptry Neck Protein Homologous to TgRON4, a Component of the Moving Junction in Toxoplasma gondii , 2006, Eukaryotic Cell.

[100]  Dave Richard,et al.  A Conserved Molecular Motor Drives Cell Invasion and Gliding Motility across Malaria Life Cycle Stages and Other Apicomplexan Parasites* , 2006, Journal of Biological Chemistry.

[101]  M. Reid,et al.  Glycophorin C is the receptor for the Plasmodium falciparum erythrocyte binding ligand PfEBP-2 (baebl). , 2003, Blood.

[102]  A. Holder,et al.  Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. , 1996, The Journal of infectious diseases.

[103]  Matthew Bogyo,et al.  Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. , 2008, Nature chemical biology.

[104]  H. Bujard,et al.  A multifunctional serine protease primes the malaria parasite for red blood cell invasion , 2009, The EMBO journal.

[105]  Dominique Soldati-Favre,et al.  Functional dissection of the apicomplexan glideosome molecular architecture. , 2010, Cell host & microbe.

[106]  J. Stephenson World health report. , 2004, Lancet.

[107]  J. Boothroyd,et al.  The C-Terminus of Toxoplasma RON2 Provides the Crucial Link between AMA1 and the Host-Associated Invasion Complex , 2011, PLoS pathogens.

[108]  J. Moulds Understanding the Knops Blood Group and its Role in Malaria , 2002, Vox sanguinis.

[109]  J. Rayner,et al.  Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[110]  L. Miller,et al.  The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. , 1976, The New England journal of medicine.

[111]  Brian J. Smith,et al.  Insights into Duffy Binding-like Domains through the Crystal Structure and Function of the Merozoite Surface Protein MSPDBL2 from Plasmodium falciparum* , 2012, The Journal of Biological Chemistry.