Home LiteratureArticle Details
PMID: 18974882 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity.

PLoS pathogens ·Vol. 4 ·No. 10 ·2008-10-00 ·Pages e1000195

Lasonder E, Janse CJ, van Gemert GJ, Mair GR, Vermunt AM, Douradinha BG, van Noort V, Huynen MA, Luty AJ, Kroeze H, Khan SM, Sauerwein RW, Waters AP, Mann M, Stunnenberg HG

Abstract

Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito -- early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans.

MeSH Terms
Animals Anopheles/parasitology Databases, Genetic Humans Malaria, Falciparum/parasitology Mice Mice, Knockout Oocysts/chemistry,growth & development Plasmodium berghei/chemistry,genetics,growth & development Plasmodium falciparum/chemistry,genetics,growth & development,pathogenicity Proteome/analysis Proteomics Protozoan Proteins/analysis,genetics Salivary Glands/parasitology Sporozoites/chemistry,growth & development
Chemicals
Proteome Protozoan Proteins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Lasonder Edwin
Department of Molecular Biology, NCMLS, Radboud University Nijmegen, Nijmegen, The Netherlands.
Janse Chris J
van Gemert Geert-Jan
Mair Gunnar R
Vermunt Adriaan M W
Douradinha Bruno G
van Noort Vera
Huynen Martijn A
Luty Adrian J F
Kroeze Hans
Khan Shahid M
Sauerwein Robert W
Waters Andrew P
Mann Matthias
Stunnenberg Hendrik G
References (87)
87 references, click to expand
  1. Sporozoite and liver stage antigen Plasmodium falciparum peptides bind specifically to human hepatocytes.
    Vaccine. 2004 Mar 12;22(9-10):1150-6 PMID: 15003642
  2. A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocysts.
    J Exp Med. 2005 Jul 18;202(2):225-30 PMID: 16027235
  3. Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3022-7 PMID: 15699336
  4. Preerythrocytic malaria vaccine development.
    Curr Opin Infect Dis. 2007 Oct;20(5):461-6 PMID: 17762778
  5. Exit of Plasmodium sporozoites from oocysts is an active process that involves the circumsporozoite protein.
    PLoS Pathog. 2005 Sep;1(1):e9 PMID: 16201021
  6. A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle.
    Mol Biochem Parasitol. 2004 Sep;137(1):23-33 PMID: 15279948
  7. Shotgun DNA microarrays and stage-specific gene expression in Plasmodium falciparum malaria.
    Mol Microbiol. 2000 Jan;35(1):6-14 PMID: 10632873
  8. PfSPATR, a Plasmodium falciparum protein containing an altered thrombospondin type I repeat domain is expressed at several stages of the parasite life cycle and is the target of inhibitory antibodies.
    J Biol Chem. 2003 Jul 11;278(28):25977-81 PMID: 12716913
  9. Migration of Plasmodium sporozoites through cells before infection.
    Science. 2001 Jan 5;291(5501):141-4 PMID: 11141568
  10. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine.
    Nature. 2005 Jan 13;433(7022):164-7 PMID: 15580261
  11. TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites.
    Cell. 1997 Aug 8;90(3):511-22 PMID: 9267031
  12. Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria.
    PLoS Pathog. 2006 Oct;2(10):e113 PMID: 17040128
  13. Exploring the transcriptome of the malaria sporozoite stage.
    Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9895-900 PMID: 11493695
  14. Getting infectious: formation and maturation of Plasmodium sporozoites in the Anopheles vector.
    Cell Microbiol. 2006 Oct;8(10):1547-56 PMID: 16984410
  15. MAEBL is essential for malarial sporozoite infection of the mosquito salivary gland.
    J Exp Med. 2002 May 20;195(10):1317-23 PMID: 12021311
  16. A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection.
    Cell Microbiol. 2005 Feb;7(2):199-208 PMID: 15659064
  17. Apicomplexan gliding motility and host cell invasion: overhauling the motor model.
    Trends Parasitol. 2004 Jan;20(1):13-6 PMID: 14700584
  18. Protein abundance profiling of the Escherichia coli cytosol.
    BMC Genomics. 2008;9:102 PMID: 18304323
  19. Differential transcriptome profiling identifies Plasmodium genes encoding pre-erythrocytic stage-specific proteins.
    Mol Microbiol. 2004 Mar;51(5):1221-32 PMID: 14982620
  20. Infectivity-associated changes in the transcriptional repertoire of the malaria parasite sporozoite stage.
    J Biol Chem. 2002 Nov 1;277(44):41948-53 PMID: 12177071
  21. A proteomic view of the Plasmodium falciparum life cycle.
    Nature. 2002 Oct 3;419(6906):520-6 PMID: 12368866
  22. Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry.
    Nature. 2002 Oct 3;419(6906):537-42 PMID: 12368870
  23. Intracellular parasite invasion strategies.
    Science. 2004 Apr 9;304(5668):248-53 PMID: 15073368
  24. A malaria scavenger receptor-like protein essential for parasite development.
    Mol Microbiol. 2002 Sep;45(6):1473-84 PMID: 12354219
  25. A surface phospholipase is involved in the migration of plasmodium sporozoites through cells.
    J Biol Chem. 2005 Feb 25;280(8):6752-60 PMID: 15590623
  26. Manipulating the Plasmodium genome.
    Curr Issues Mol Biol. 2005 Jan;7(1):39-55 PMID: 15580779
  27. Migration through host cells: the first steps of Plasmodium sporozoites in the mammalian host.
    Cell Microbiol. 2004 Dec;6(12):1113-8 PMID: 15527491
  28. A multidomain adhesion protein family expressed in Plasmodium falciparum is essential for transmission to the mosquito.
    J Exp Med. 2004 Jun 7;199(11):1533-44 PMID: 15184503
  29. Liver invasion by malarial parasites--how do malarial parasites break through the host barrier?
    Cell Microbiol. 2004 Dec;6(12):1119-25 PMID: 15527492
  30. A conserved U-rich RNA region implicated in regulation of translation in Plasmodium female gametocytes.
    Nucleic Acids Res. 2008 Mar;36(4):1176-86 PMID: 18158300
  31. Serial analysis of gene expression in Plasmodium falciparum reveals the global expression profile of erythrocytic stages and the presence of anti-sense transcripts in the malarial parasite.
    Mol Biol Cell. 2001 Oct;12(10):3114-25 PMID: 11598196
  32. Demonstration of heat-shock protein 70 in the sporozoite stage of malaria parasites.
    Parasitol Res. 1994;80(1):16-21 PMID: 8153120
  33. Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites.
    J Cell Sci. 2003 Jan 1;116(Pt 1):39-49 PMID: 12456714
  34. Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases: implications for vaccine and drug design.
    Infect Immun. 2007 Dec;75(12):5565-74 PMID: 17893128
  35. Genetically modified Plasmodium highlights the potential of whole parasite vaccine strategies.
    Trends Immunol. 2005 Jun;26(6):295-7 PMID: 15922944
  36. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein.
    Mol Cell Proteomics. 2005 Sep;4(9):1265-72 PMID: 15958392
  37. Analysis of the Plasmodium and Anopheles transcriptomes during oocyst differentiation.
    J Biol Chem. 2004 Feb 13;279(7):5581-7 PMID: 14627711
  38. CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts.
    Mol Microbiol. 2006 Mar;59(5):1369-79 PMID: 16468982
  39. Regulation of sexual development of Plasmodium by translational repression.
    Science. 2006 Aug 4;313(5787):667-9 PMID: 16888139
  40. Migration through host cells activates Plasmodium sporozoites for infection.
    Nat Med. 2002 Nov;8(11):1318-22 PMID: 12379848
  41. Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.
    Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12194-9 PMID: 16103357
  42. Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology.
    Cell. 2005 Jun 3;121(5):675-87 PMID: 15935755
  43. GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.
    Bioinformatics. 2004 Dec 12;20(18):3710-5 PMID: 15297299
  44. Two proteins with 6-cys motifs are required for malarial parasites to commit to infection of the hepatocyte.
    Mol Microbiol. 2005 Dec;58(5):1264-75 PMID: 16313615
  45. Discovery of gene function by expression profiling of the malaria parasite life cycle.
    Science. 2003 Sep 12;301(5639):1503-8 PMID: 12893887
  46. Plasmodium falciparum sporozoite invasion is inhibited by naturally acquired or experimentally induced polyclonal antibodies to the STARP antigen.
    Eur J Immunol. 1997 Oct;27(10):2502-13 PMID: 9368603
  47. Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system.
    EMBO J. 2002 Apr 2;21(7):1597-606 PMID: 11927544
  48. Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle.
    Genome Res. 2004 Nov;14(11):2308-18 PMID: 15520293
  49. Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins demonstrates their functional redundancy.
    J Biol Chem. 2004 Dec 24;279(52):54088-96 PMID: 15491999
  50. von Willebrand Factor A domain-related protein, a novel microneme protein of the malaria ookinete highly conserved throughout Plasmodium parasites.
    Mol Biochem Parasitol. 2001 Aug;116(1):65-72 PMID: 11463467
  51. The Plasmodium TRAP/MIC2 family member, TRAP-Like Protein (TLP), is involved in tissue traversal by sporozoites.
    Cell Microbiol. 2008 Jul;10(7):1505-16 PMID: 18346224
  52. A combined transcriptome and proteome survey of malaria parasite liver stages.
    Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):305-10 PMID: 18172196
  53. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks.
    Bioinformatics. 2005 Aug 15;21(16):3448-9 PMID: 15972284
  54. PlasmoDB: the Plasmodium genome resource. An integrated database providing tools for accessing, analyzing and mapping expression and sequence data (both finished and unfinished).
    Nucleic Acids Res. 2002 Jan 1;30(1):87-90 PMID: 11752262
  55. Depletion of the Plasmodium berghei thrombospondin-related sporozoite protein reveals a role in host cell entry by sporozoites.
    Mol Biochem Parasitol. 2007 Jun;153(2):158-66 PMID: 17418435
  56. Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer.
    PLoS Biol. 2004 Jan;2(1):E4 PMID: 14737184
  57. Cytoskeleton of apicomplexan parasites.
    Microbiol Mol Biol Rev. 2002 Mar;66(1):21-38; table of contents PMID: 11875126
  58. A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites.
    J Biol Chem. 2004 Mar 5;279(10):9490-6 PMID: 14676185
  59. Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum.
    Mol Biochem Parasitol. 2006 Oct;149(2):216-22 PMID: 16824624
  60. Trypsin cleaves exclusively C-terminal to arginine and lysine residues.
    Mol Cell Proteomics. 2004 Jun;3(6):608-14 PMID: 15034119
  61. A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses.
    Science. 2005 Jan 7;307(5706):82-6 PMID: 15637271
  62. Selection of Anopheles stephensi for refractoriness and susceptibility to Plasmodium falciparum.
    Med Vet Entomol. 1989 Jan;3(1):41-52 PMID: 2519646
  63. High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei.
    Nat Protoc. 2006;1(1):346-56 PMID: 17406255
  64. Vaccination against malaria with live parasites.
    Expert Rev Vaccines. 2006 Aug;5(4):473-81 PMID: 16989628
  65. The Plasmodium falciparum knob-associated PfEMP3 antigen is also expressed at pre-erythrocytic stages and induces antibodies which inhibit sporozoite invasion.
    Mol Biochem Parasitol. 2001 Feb;112(2):253-61 PMID: 11223132
  66. Co-ordinated programme of gene expression during asexual intraerythrocytic development of the human malaria parasite Plasmodium falciparum revealed by microarray analysis.
    Mol Microbiol. 2001 Jan;39(1):26-36 PMID: 11123685
  67. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes.
    Nature. 1997 Jan 23;385(6614):336-40 PMID: 9002517
  68. Integrative analysis of intraerythrocytic differentially expressed transcripts yields novel insights into the biology of Plasmodium falciparum.
    Malar J. 2003 Nov 14;2(1):38 PMID: 14617379
  69. Plasmodium cysteine repeat modular proteins 1-4: complex proteins with roles throughout the malaria parasite life cycle.
    Cell Microbiol. 2007 Jun;9(6):1466-80 PMID: 17253978
  70. Ranking: a closer look on globalisation methods for normalisation of gene expression arrays.
    Nucleic Acids Res. 2002 Jun 1;30(11):e50 PMID: 12034851
  71. New concepts in vaccine development in malaria.
    Curr Opin Infect Dis. 2007 Jun;20(3):311-6 PMID: 17471043
  72. A long and winding road: the Plasmodium sporozoite's journey in the mammalian host.
    Parasitol Int. 2007 Sep;56(3):171-8 PMID: 17513164
  73. A central role for P48/45 in malaria parasite male gamete fertility.
    Cell. 2001 Jan 12;104(1):153-64 PMID: 11163248
  74. Evidence-based annotation of the malaria parasite's genome using comparative expression profiling.
    PLoS One. 2008;3(2):e1570 PMID: 18270564
  75. Plasmodium falciparum phosphoenolpyruvate carboxykinase is developmentally regulated in gametocytes.
    Mol Biochem Parasitol. 2000 Apr 15;107(2):227-40 PMID: 10779599
  76. A malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites.
    J Cell Biol. 2004 Nov 8;167(3):425-32 PMID: 15533999
  77. PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data.
    Nucleic Acids Res. 2003 Jan 1;31(1):212-5 PMID: 12519984
  78. Plasmodium biology: genomic gleanings.
    Cell. 2003 Dec 26;115(7):771-85 PMID: 14697197
  79. Nomadic or sessile: can Kupffer cells function as portals for malaria sporozoites to the liver?
    Cell Microbiol. 2006 Oct;8(10):1537-46 PMID: 16911567
  80. Selection by flow-sorting of genetically transformed, GFP-expressing blood stages of the rodent malaria parasite, Plasmodium berghei.
    Nat Protoc. 2006;1(2):614-23 PMID: 17406288
  81. Improved detection of overrepresentation of Gene-Ontology annotations with parent child analysis.
    Bioinformatics. 2007 Nov 15;23(22):3024-31 PMID: 17848398
  82. The elusive malaria sporozoite in the mammalian host.
    Mol Microbiol. 2004 Oct;54(2):298-306 PMID: 15469504
  83. Serial Analysis of Gene Expression in Plasmodium berghei salivary gland sporozoites.
    BMC Genomics. 2007;8:466 PMID: 18093287
  84. Characterization of Plasmodium falciparum sporozoite surface protein 2.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9176-80 PMID: 1409621
  85. Sporozoite load of mosquitoes infected with Plasmodium falciparum.
    Trans R Soc Trop Med Hyg. 1989 Jan-Feb;83(1):67-70 PMID: 2690418
  86. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.
    PLoS Biol. 2003 Oct;1(1):E5 PMID: 12929205
  87. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes.
    Parasitology. 1989 Apr;98 Pt 2:165-73 PMID: 2668861
Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000195
Published
2008-10-00
Epub
2008-00-31
Pages
e1000195
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC2570797
Subset
IM
Grants
Wellcome Trust · United Kingdom
Wellcome Trust · 083811 · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.ppat.1000195 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2