Proteomic analysis of Plasmodium in the mosquito: progress and pitfalls

SUMMARY Here we discuss proteomic analyses of whole cell preparations of the mosquito stages of malaria parasite development (i.e. gametocytes, microgamete, ookinete, oocyst and sporozoite) of Plasmodium berghei. We also include critiques of the proteomes of two cell fractions from the purified ookinete, namely the micronemes and cell surface. Whereas we summarise key biological interpretations of the data, we also try to identify key methodological constraints we have met, only some of which we were able to resolve. Recognising the need to translate the potential of current genome sequencing into functional understanding, we report our efforts to develop more powerful combinations of methods for the in silico prediction of protein function and location. We have applied this analysis to the proteome of the male gamete, a cell whose very simple structural organisation facilitated interpretation of data. Some of the in silico predictions made have now been supported by ongoing protein tagging and genetic knockout studies. We hope this discussion may assist future studies.

[1]  R. Stephens,et al.  Attachment and Entry of Chlamydia Have Distinct Requirements for Host Protein Disulfide Isomerase , 2009, PLoS pathogens.

[2]  P. Jenoe,et al.  Neospora caninum protein disulfide isomerase is involved in tachyzoite-host cell interaction. , 2005, International journal for parasitology.

[3]  John R Yates,et al.  A Comprehensive Survey of the Plasmodium Life Cycle by Genomic, Transcriptomic, and Proteomic Analyses , 2005, Science.

[4]  Daisuke Kihara,et al.  Enhanced automated function prediction using distantly related sequences and contextual association by PFP , 2006, Protein science : a publication of the Protein Society.

[5]  R. Ménard,et al.  PbGEST mediates malaria transmission to both mosquito and vertebrate host , 2011, Molecular microbiology.

[6]  R. Edwards,et al.  Extra-nuclear location of histones in activated human peripheral blood lymphocytes and cultured T-cells. , 1995, Biochemical pharmacology.

[7]  F. Cohen,et al.  Expression profiling of the schizont and trophozoite stages of Plasmodium falciparum with a long-oligonucleotide microarray , 2003, Genome Biology.

[8]  D. Carucci,et al.  Functional proteome and expression analysis of sporozoites and hepatic stages of malaria development. , 2005, Current topics in microbiology and immunology.

[9]  W. A. Krotoski Discovery of the hypnozoite and a new theory of malarial relapse. , 1985, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[10]  Stuart M. Brown,et al.  Transcriptome of axenic liver stages of Plasmodium yoelii. , 2004, Molecular and biochemical parasitology.

[11]  J. C. Yang,et al.  Isolation of merozoite rhoptries, identification of novel rhoptry-associated proteins from Plasmodium yoelii, P. chabaudi, P. berghei, and conserved interspecies reactivity of organelles and proteins with P. falciparum rhoptry-specific antibodies. , 1998, Experimental parasitology.

[12]  R. Sinden The cell biology of sexual development in Plasmodium , 1983, Parasitology.

[13]  R. Sinden,et al.  Members of a trypsin gene family in Anopheles gambiae are induced in the gut by blood meal. , 1993, The EMBO journal.

[14]  John R Yates,et al.  Proteome analysis of rhoptry-enriched fractions isolated from Plasmodium merozoites. , 2004, Journal of proteome research.

[15]  R. Sinden,et al.  Structure and expression of a post-transcriptionally regulated malaria gene encoding a surface protein from the sexual stages of Plasmodium berghei. , 1993, Molecular and biochemical parasitology.

[16]  Neil Hall,et al.  Regulation of Sexual Development of Plasmodium by Translational Repression , 2006, Science.

[17]  G. McFadden,et al.  Apicoplast and Mitochondrion in Gametocytogenesis of Plasmodium falciparum , 2008, Eukaryotic Cell.

[18]  Elisabetta Pizzi,et al.  Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum. , 2005, Molecular and biochemical parasitology.

[19]  A. Holder,et al.  The Armadillo Repeat Protein PF16 Is Essential for Flagellar Structure and Function in Plasmodium Male Gametes , 2010, PloS one.

[20]  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.

[21]  Neil Hall,et al.  Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry , 2002, Nature.

[22]  Xinxia Peng,et al.  A combined transcriptome and proteome survey of malaria parasite liver stages , 2008, Proceedings of the National Academy of Sciences.

[23]  R. Sinden,et al.  In situ detection of Pbs21 mRNA during sexual development of Plasmodium berghei. , 1994, Molecular and biochemical parasitology.

[24]  C. Janse,et al.  Plasmodium post-genomics: better the bug you know? , 2006, Nature Reviews Microbiology.

[25]  R. Carter,et al.  Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum , 2004, Current Genetics.

[26]  Jenn-Kang Hwang,et al.  Prediction of protein subcellular localization , 2006, Proteins.

[27]  J. E. Hyde,et al.  Proteomics of the human malaria parasite Plasmodium falciparum , 2006, Expert review of proteomics.

[28]  Benhur Lee,et al.  Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry , 2011, Proceedings of the National Academy of Sciences.

[29]  Christine A. Orengo,et al.  FFPred: an integrated feature-based function prediction server for vertebrate proteomes , 2008, Nucleic Acids Res..

[30]  Hagit Shatkay,et al.  SherLoc2: a high-accuracy hybrid method for predicting subcellular localization of proteins. , 2009, Journal of proteome research.

[31]  J. Adams,et al.  Exploring the transcriptome of the malaria sporozoite stage , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Paul M Southworth,et al.  A mass spectrometric strategy for absolute quantification of Plasmodium falciparum proteins of low abundance , 2011, Malaria Journal.

[33]  Paul Horton,et al.  Nucleic Acids Research Advance Access published May 21, 2007 WoLF PSORT: protein localization predictor , 2007 .

[34]  Yeates Ra,et al.  In vitro damage of cultured ookinetes of Plasmodium gallinaceum by digestive proteinases from susceptible Aedes aegypti. , 1979 .

[35]  R. Gass Influences of blood digestion on the development of Plasmodium gallinaceum (Brumpt) in the midgut of Aedes aegypti (L.). , 1977, Acta tropica.

[36]  Zbynek Bozdech,et al.  Quantitative Time-course Profiling of Parasite and Host Cell Proteins in the Human Malaria Parasite Plasmodium falciparum* , 2011, Molecular & Cellular Proteomics.

[37]  Joanne M. Morrisey,et al.  Branched tricarboxylic acid metabolism in Plasmodium falciparum , 2011, Nature.

[38]  S. Brunak,et al.  Locating proteins in the cell using TargetP, SignalP and related tools , 2007, Nature Protocols.

[39]  Michael J. E. Sternberg,et al.  3DLigandSite: predicting ligand-binding sites using similar structures , 2010, Nucleic Acids Res..

[40]  K. Matuschewski,et al.  Critical role for a stage‐specific actin in male exflagellation of the malaria parasite , 2011, Cellular microbiology.

[41]  G. von Heijne,et al.  Prediction of membrane-protein topology from first principles , 2008, Proceedings of the National Academy of Sciences.

[42]  C. Lavazec,et al.  PfCCp proteins of Plasmodium falciparum: gametocyte-specific expression and role in complement-mediated inhibition of exflagellation. , 2008, International journal for parasitology.

[43]  Chris J Janse,et al.  Localisation and timing of expression of putative Plasmodium berghei rhoptry proteins in merozoites and sporozoites. , 2009, Molecular and biochemical parasitology.

[44]  Y. Han,et al.  Implications of Time Bomb model of ookinete invasion of midgut cells. , 2002, Insect biochemistry and molecular biology.

[45]  Joseph L. DeRisi,et al.  Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum , 2011, PLoS biology.

[46]  J. Yates,et al.  Exploring the proteome of Plasmodium. , 2002, International journal for parasitology.

[47]  R. Sinden,et al.  Gametogenesis and fertilization in Plasmodium yoelii nigeriensis: a transmission electron microscope study , 1976, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[48]  D. Fidock,et al.  Vesicular ATPase-overexpressing Cells Determine the Distribution of Malaria Parasite Oocysts on the Midguts of Mosquitoes* , 1999, The Journal of Biological Chemistry.

[49]  A. Pain,et al.  Transition of Plasmodium Sporozoites into Liver Stage-Like Forms Is Regulated by the RNA Binding Protein Pumilio , 2011, PLoS pathogens.

[50]  V. Klaren,et al.  Conserved regions of protein disulfide isomerase are targeted by natural IgA antibodies in humans. , 2002, International immunology.

[51]  L. Miller,et al.  Invasion of erythrocytes by malaria parasites: erythrocyte ligands and parasite receptors. , 1988, Progress in allergy.

[52]  J. Martínez-Barnetche,et al.  Conserved peptide sequences bind to actin and enolase on the surface of Plasmodium berghei ookinetes , 2011, Parasitology.

[53]  John R Yates,et al.  Characterisation of Plasmodium invasive organelles; an ookinete microneme proteome , 2009, Proteomics.

[54]  R. Gass,et al.  In vitro damage of cultured ookinetes of Plasmodium gallinaceum by digestive proteinases from susceptible Aedes aegypti. , 1979, Acta tropica.

[55]  Joshua E Elias,et al.  The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries. , 2011, Cell host & microbe.

[56]  A. Waters,et al.  Gene expression in Plasmodium berghei ookinetes and early oocysts in a co-culture system with mosquito cells. , 2005, Molecular and biochemical parasitology.

[57]  Robert D. Finn,et al.  New developments in the InterPro database , 2007, Nucleic Acids Res..

[58]  K. Chou,et al.  Euk-mPLoc: a fusion classifier for large-scale eukaryotic protein subcellular location prediction by incorporating multiple sites. , 2007, Journal of proteome research.

[59]  Gajendra P. S. Raghava,et al.  ESLpred2: improved method for predicting subcellular localization of eukaryotic proteins , 2008, BMC Bioinformatics.

[60]  John E Hyde,et al.  Quantitative proteomics of the human malaria parasite Plasmodium falciparum and its application to studies of development and inhibition , 2004, Molecular microbiology.

[61]  Erik L. L. Sonnhammer,et al.  Predicting protein function from domain content , 2008, Bioinform..

[62]  M. Mota,et al.  Use of a Selective Inhibitor To Define the Chemotherapeutic Potential of the Plasmodial Hexose Transporter in Different Stages of the Parasite's Life Cycle , 2011, Antimicrobial Agents and Chemotherapy.

[63]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[64]  Martijn A. Huynen,et al.  Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity , 2008, PLoS pathogens.

[65]  Matthias Mann,et al.  Proteome Analysis of Separated Male and Female Gametocytes Reveals Novel Sex-Specific Plasmodium Biology , 2005, Cell.

[66]  R. Carter,et al.  Gamete development in malaria parasites: bicarbonate-dependent stimulation by pH in vitro , 1978, Parasitology.

[67]  R. Sinden,et al.  Gametocyte and gamete development in Plasmodium falciparum , 1978, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[68]  Jonathan E. Allen,et al.  Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii , 2002, Nature.

[69]  R. Sinden 3 – Cell Biology , 1978 .

[70]  M. Shahabuddin,et al.  Plasmodium gallinaceum preferentially invades vesicular ATPase-expressing cells in Aedes aegypti midgut. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Joanne M. Morrisey,et al.  Branched Tricarboxylic Acid Metabolism in Plasmodium falciparum , 2010, Nature.

[72]  M. Sternberg,et al.  The flagellum in malarial parasites. , 2010, Current opinion in microbiology.

[73]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[74]  Arne Elofsson,et al.  TOPCONS: consensus prediction of membrane protein topology , 2009, Nucleic Acids Res..

[75]  K. Kirk,et al.  Membrane transport proteins of the malaria parasite , 2009, Molecular microbiology.

[76]  Joshua E. Elias,et al.  Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. , 2003, Journal of proteome research.

[77]  David L. Tabb,et al.  A proteomic view of the Plasmodium falciparum life cycle , 2002, Nature.

[78]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[79]  Robert D. Finn,et al.  InterPro: the integrative protein signature database , 2008, Nucleic Acids Res..

[80]  John Sidney,et al.  Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[81]  M. Sternberg,et al.  Protein structure prediction on the Web: a case study using the Phyre server , 2009, Nature Protocols.

[82]  T. Wells,et al.  New medicines to improve control and contribute to the eradication of malaria , 2010, Malaria Journal.

[83]  Michael J. E. Sternberg,et al.  ConFunc - functional annotation in the twilight zone , 2008, Bioinform..

[84]  Amos Bairoch,et al.  The ENZYME data bank in 1999 , 1999, Nucleic Acids Res..

[85]  C. Janse,et al.  Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum. , 2006, Molecular and biochemical parasitology.