Proteomic analysis of zygote and ookinete stages of the avian malaria parasite Plasmodium gallinaceum delineates the homologous proteomes of the lethal human malaria parasite Plasmodium falciparum

Delineation of the complement of proteins comprising the zygote and ookinete, the early developmental stages of Plasmodium within the mosquito midgut, is fundamental to understand initial molecular parasite‐vector interactions. The published proteome of Plasmodium falciparum does not include analysis of the zygote/ookinete stages, nor does that of P. berghei include the zygote stage or secreted proteins. P. gallinaceum zygote, ookinete, and ookinete‐secreted/released protein samples were prepared and subjected to Multidimensional protein identification technology (MudPIT). Peptides of P. gallinaceum zygote, ookinete, and ookinete‐secreted proteins were identified by MS/MS, mapped to ORFs (>50 amino acids) in the extent P. gallinaceum whole genome sequence, and then matched to homologous ORFs in P. falciparum. A total of 966 P. falciparum ORFs encoding orthologous proteins were identified; just over 40% of these predicted proteins were found to be hypothetical. A majority of putative proteins with predicted secretory signal peptides or transmembrane domains were hypothetical proteins. This analysis provides a more comprehensive view of the hitherto unknown proteome of the early mosquito midgut stages of P. falciparum. The results underpin more robust study of Plasmodium–mosquito midgut interactions, fundamental to the development of novel strategies of blocking malaria transmission.

[1]  K. Patra,et al.  An anti-Chitinase malaria transmission-blocking single-chain antibody as an effector molecule for creating a Plasmodium falciparum-refractory mosquito. , 2005, The Journal of infectious diseases.

[2]  John R Yates,et al.  Quantitative phosphoproteomic analysis of the tumor necrosis factor pathway. , 2006, Journal of proteome research.

[3]  J. Vinetz,et al.  Identification of Novel Plasmodium gallinaceum Zygote- and Ookinete-Expressed Proteins as Targets for Blocking Malaria Transmission , 2002, Infection and Immunity.

[4]  E. Cabib,et al.  Malaria parasite chitinase and penetration of the mosquito peritrophic membrane. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. Kaslow,et al.  Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Sinden A proteomic analysis of malaria biology: integration of old literature and new technologies. , 2004, International journal for parasitology.

[7]  J. Dame,et al.  Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. , 1984, Science.

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

[9]  F. Kafatos,et al.  The developmental migration of Plasmodium in mosquitoes. , 2006, Current opinion in genetics & development.

[10]  F J Ayala,et al.  Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

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

[12]  D. Kaslow,et al.  The peritrophic membrane as a barrier: its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes. , 1991, Experimental parasitology.

[13]  R. Carter,et al.  Characterization of antigens on mosquito midgut stages of Plasmodium gallinaceum. II. Comparison of surface antigens of male and female gametes and zygotes. , 1984, Molecular and biochemical parasitology.

[14]  R. Hayward,et al.  The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Vinetz,et al.  Plasmodium ookinete invasion of the mosquito midgut. , 2005, Current topics in microbiology and immunology.

[16]  T. Tsuboi,et al.  Plasmodium Ookinete-secreted Proteins Secreted through a Common Micronemal Pathway Are Targets of Blocking Malaria Transmission* , 2004, Journal of Biological Chemistry.

[17]  J. Yates,et al.  Large-scale analysis of the yeast proteome by multidimensional protein identification technology , 2001, Nature Biotechnology.

[18]  A. Lensen,et al.  Mechanisms that reduce transmission of Plasmodium falciparum malaria in semiimmune and nonimmune persons. , 1998, The Journal of infectious diseases.

[19]  R. Sinden,et al.  Plasmodium invasion of mosquito cells: hawk or dove? , 2001, Trends in parasitology.

[20]  J. Yates,et al.  DTASelect and Contrast: tools for assembling and comparing protein identifications from shotgun proteomics. , 2002, Journal of proteome research.

[21]  Rafael Cantera,et al.  Real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion. , 2004, Cellular microbiology.

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

[23]  F. Kafatos,et al.  Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes , 2000, The EMBO journal.

[24]  F. Ayala,et al.  Evolutionary origin of Plasmodium and other Apicomplexa based on rRNA genes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[26]  J. Sachs,et al.  The economic and social burden of malaria , 2002, Nature.

[27]  L. Aravind,et al.  Chitinases of the Avian Malaria Parasite Plasmodium gallinaceum, a Class of Enzymes Necessary for Parasite Invasion of the Mosquito Midgut* , 2000, The Journal of Biological Chemistry.

[28]  D. Higgins,et al.  Plasmodium falciparum appears to have arisen as a result of lateral transfer between avian and human hosts. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Patricia De la Vega,et al.  Discovery of Gene Function by Expression Profiling of the Malaria Parasite Life Cycle , 2003, Science.

[30]  J. Yates,et al.  Shotgun Proteomics and Biomarker Discovery , 2002, Disease markers.

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