Skip to main content

Advertisement

SpringerLink
Log in

Identification and expression of maebl, an erythrocyte-binding gene, in Plasmodium gallinaceum

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Avian malaria is of significant ecological importance and serves as a model system to study broad patterns of host switching and host specificity. The erythrocyte invasion mechanism of the malaria parasite Plasmodium is mediated, in large part, by proteins of the erythrocyte-binding-like (ebl) family of genes. However, little is known about how these genes are conserved across different species of Plasmodium, especially those that infect birds. Using bioinformatical methods in conjunction with polymerase chain reaction (PCR) and genetic sequencing, we identified and annotated one member of the ebl family, merozoite apical erythrocyte-binding ligand (maebl), from the chicken parasite Plasmodium gallinaceum. We then detected the expression of maebl in P. gallinaceum by PCR analysis of cDNA isolated from the blood of infected chickens. We found that maebl is a conserved orthologous gene in avian, mammalian, and rodent Plasmodium species. The duplicate extracellular binding domains of MAEBL, responsible for erythrocyte binding, are the most conserved regions. Our combined data corroborate the conservation of maebl throughout the Plasmodium genus and may help elucidate the mechanisms of erythrocyte invasion in P. gallinaceum and the host specificity of Plasmodium parasites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

MAEBL:

Merozoite apical erythrocyte-binding ligand

EBA-175:

Erythrocyte-binding antigen-175

DBP:

Duffy-binding protein

EBL:

Erythrocyte binding-like

PCR:

Polymerase chain reaction

RBC:

Red blood cells

EST:

Expressed sequence tags

References

  • Adams JH, Blair PL, Kaneko O, Peterson DS (2001) An expanding ebl family of Plasmodium falciparum. Trends Parasitol 17:297–299

    Article  PubMed  CAS  Google Scholar 

  • Adams JH, Sim BK, Dolan SA, Fang X, Kaslow DC, Miller LH (1992) A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 89:7085–7089

    Article  PubMed  CAS  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  • Balu B, Blair PL, Adams JH (2009) Identification of the transcription initiation site reveals a novel transcript structure for Plasmodium falciparum maebl. Exp Parasitol 121:110–114

    Article  PubMed  CAS  Google Scholar 

  • Beadell JS, Covas R, Gebhard C, Ishtiaq F, Melo M, Schmidt BK, Perkins SL, Graves GR, Fleischer RC (2009) Host associations and evolutionary relationships of avian blood parasites from West Africa. Int J Parasitol 39:257–266

    Article  PubMed  Google Scholar 

  • Blair PL, Kappe SH, Maciel JE, Balu B, Adams JH (2002) Plasmodium falciparum MAEBL is a unique member of the ebl family. Mol Biochem Parasitol 122:35–44

    Article  PubMed  CAS  Google Scholar 

  • Brown A, Higgins MK (2010) Carbohydrate binding molecules in malaria pathology. Curr Opin Struct Biol 20:560–566

    Article  PubMed  CAS  Google Scholar 

  • Cantarel BL, Korf I, Robb SM, Parra G, Ross E, Moore B, Holt C, Sanchez Alvarado A, Yandell M (2008) MAKER: an easy-to-use annotation pipeline designed for emerging model organism genomes. Genome Res 18:188–196

    Article  PubMed  CAS  Google Scholar 

  • Chattopadhyay D, Rayner J, McHenry AM, Adams JH (2006) The structure of the Plasmodium falciparum EBA175 ligand domain and the molecular basis of host specificity. Trends Parasitol 22:143–145

    Article  PubMed  CAS  Google Scholar 

  • Chesne-Seck ML, Pizarro JC, Vulliez-Le Normand B, Collins CR, Blackman MJ, Faber BW, Remarque EJ, Kocken CH, Thomas AW, Bentley GA (2005) Structural comparison of apical membrane antigen 1 orthologues and paralogues in apicomplexan parasites. Mol Biochem Parasitol 144:55–67

    Article  PubMed  CAS  Google Scholar 

  • Chitnis CE, Blackman MJ (2000) Host cell invasion by malaria parasites. Parasitol Today 16:411–415

    Article  PubMed  CAS  Google Scholar 

  • Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Durainsingh MT, Rayner JC, Wright GJ (2011) Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 480:534–7

    Google Scholar 

  • Drummond PB, Peterson DS (2005) An analysis of genetic diversity within the ligand domains of the Plasmodium falciparum ebl-1 gene. Mol Biochem Parasitol 140:241–245

    Article  PubMed  CAS  Google Scholar 

  • Duk M, Krotkiewski H, Stasyk TV, Lutsik-Kordovsky M, Syper D, Lisowska E (2000) Isolation and characterization of glycophorin from nucleated (chicken) erythrocytes. Arch Biochem Biophys 375:111–118

    Article  PubMed  CAS  Google Scholar 

  • Florens L, Washburn MP, Raine JD, Anthony RM, Grainger M, Haynes JD, Moch JK, Muster N, Sacci JB, Tabb DL, Witney AA, Wolters D, Wu Y, Gardner MJ, Holder AA, Sinden RE, Yates JR, Carucci DJ (2002) A proteomic view of the Plasmodium falciparum life cycle. Nature 419:520–526

    Article  PubMed  CAS  Google Scholar 

  • Frevert U, Spath GF, Yee H (2008) Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken. Int J Parasitol 38:655–672

    Article  PubMed  CAS  Google Scholar 

  • Fu J, Saenz F, Reed MB, Balu B, Singh N, Blair PL, Cowman AF, Adams JH (2005) Targeted disruption of maebl in Plasmodium falciparum. Mol Biochem Parasitol 141:113–117

    Article  PubMed  CAS  Google Scholar 

  • Garamszegi LZ (2006) The evolution of virulence and host specialization in malaria parasites of primates. Ecol Lett 9:933–940

    Article  PubMed  Google Scholar 

  • Ghai M, Dutta S, Hall T, Freilich D, Ockenhouse CF (2002) Identification, expression, and functional characterization of MAEBL, a sporozoite and asexual blood stage chimeric erythrocyte-binding protein of Plasmodium falciparum. Mol Biochem Parasitol 123:35–45

    Article  PubMed  CAS  Google Scholar 

  • Huelsenbeck JP, Ronquist F, Nielsen R, Bollback JP (2001) Bayesian inference of phylogeny and its impact on evolutionary biology. Science 294:2310–2314

    Article  PubMed  CAS  Google Scholar 

  • Iezhova TA, Valkiunas G, Bairlein F (2005) Vertebrate host specificity of two avian malaria parasites of the subgenus Novyella: Plasmodium nucleophilum and Plasmodium vaughani. J Parasitol 91:472–474

    Article  PubMed  Google Scholar 

  • Iyer J, Gruner AC, Renia L, Snounou G, Preiser PR (2007) Invasion of host cells by malaria parasites: a tale of two protein families. Mol Microbiol 65:231–249

    Article  PubMed  CAS  Google Scholar 

  • Kappe SH, Noe AR, Fraser TS, Blair PL, Adams JH (1998) A family of chimeric erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 95:1230–1235

    Article  PubMed  CAS  Google Scholar 

  • Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948

    Article  PubMed  CAS  Google Scholar 

  • Lewis SE, Searle SM, Harris N, Gibson M, Lyer V, Richter J, Wiel C, Bayraktaroglir L, Birney E, Crosby MA, Kaminker JS, Matthews BB, Prochnik SE, Smithy CD, Tupy JL, Rubin GM, Misra S, Mungall CJ, Clamp ME (2002) Apollo: a sequence annotation editor. Genome Biol 3. RESEARCH0082

  • Loiseau C, Harrigan RJ, Robert A, Bowie RC, Thomassen HA, Smith TB, Sehgal RN (2012) Host and habitat specialization of avian malaria in Africa. Mol Ecol 21:431–441

    Article  PubMed  Google Scholar 

  • Loiseau C, Iezhova T, Valkiunas G, Chasar A, Hutchinson A, Buermann W, Smith TB, Sehgal RN (2010) Spatial variation of haemosporidian parasite infection in African rainforest bird species. J Parasitol 96:21–29

    Article  PubMed  Google Scholar 

  • Martin MJ, Rayner JC, Gagneux P, Barnwell JW, Varki A (2005) Evolution of human–chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid. Proc Natl Acad Sci USA 102:12819–12824

    Article  PubMed  CAS  Google Scholar 

  • Martinsen ES, Perkins SL, Schall JJ (2008) A three-genome phylogeny of malaria parasites (Plasmodium and closely related genera): evolution of life-history traits and host switches. Mol Phylogenet Evol 47:261–273

    Article  PubMed  CAS  Google Scholar 

  • Mayer DC, Cofie J, Jiang L, Hartl DL, Tracy E, Kabat J, Mendoza LH, Miller LH (2009) Glycophorin B is the erythrocyte receptor of Plasmodium falciparum erythrocyte-binding ligand, EBL-1. Proc Natl Acad Sci USA 106:5348–5352

    Article  PubMed  CAS  Google Scholar 

  • Michon P, Stevens JR, Kaneko O, Adams JH (2002) Evolutionary relationships of conserved cysteine-rich motifs in adhesive molecules of malaria parasites. Mol Biol Evol 19:1128–1142

    Article  PubMed  CAS  Google Scholar 

  • Nagao E, Arie T, Dorward DW, Fairhurst RM, Dvorak JA (2008) The avian malaria parasite Plasmodium gallinaceum causes marked structural changes on the surface of its host erythrocyte. J Struct Biol 162:460–467

    Article  PubMed  CAS  Google Scholar 

  • Noe AR, Adams JH (1998) Plasmodium yoelii YM MAEBL protein is coexpressed and colocalizes with rhoptry proteins. Mol Biochem Parasitol 96:27–35

    Article  PubMed  CAS  Google Scholar 

  • Orlandi PA, Klotz FW, Haynes JD (1992) 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. J Cell Biol 116:901–909

    Article  PubMed  CAS  Google Scholar 

  • Outlaw DC, Ricklefs RE (2011) Rerooting the evolutionary tree of malaria parasites. Proc Natl Acad Sci USA 108:13183–13187

    Article  PubMed  CAS  Google Scholar 

  • Patra KP, Johnson JR, Cantin GT, Yates JR 3rd, Vinetz JM (2008) 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. Proteomics 8:2492–2499

    Article  PubMed  CAS  Google Scholar 

  • Preiser P, Renia L, Singh N, Balu B, Jarra W, Voza T, Kaneko O, Blair P, Torii M, Landau I, Adams JH (2004) Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro. Infect Immun 72:3604–3608

    Article  PubMed  CAS  Google Scholar 

  • Ricklefs RE, Outlaw DC (2010) A molecular clock for malaria parasites. Science 329:226–229

    Article  PubMed  CAS  Google Scholar 

  • Rincon-Arano H, Guerrero G, Valdes-Quezada C, Recillas-Targa F (2009) Chicken alpha-globin switching depends on autonomous silencing of the embryonic pi globin gene by epigenetics mechanisms. J Cell Biochem 108:675–687

    Article  PubMed  CAS  Google Scholar 

  • Saenz FE, Balu B, Smith J, Mendonca SR, Adams JH (2008) The transmembrane isoform of Plasmodium falciparum MAEBL is essential for the invasion of Anopheles salivary glands. PLoS One 3:e2287

    Article  PubMed  Google Scholar 

  • Silva JC, Egan A, Friedman R, Munro JB, Carlton JM, Hughes AL (2011) Genome sequences reveal divergence times of malaria parasite lineages. Parasitology 138:1737–1749

    Article  PubMed  Google Scholar 

  • Singh N, Preiser P, Renia L, Balu B, Barnwell J, Blair P, Jarra W, Voza T, Landau I, Adams JH (2004) Conservation and developmental control of alternative splicing in maebl among malaria parasites. J Mol Biol 343:589–599

    Article  PubMed  CAS  Google Scholar 

  • Suyama M, Torrents D, Bork P (2006) PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res 34:W609–W612

    Article  PubMed  CAS  Google Scholar 

  • Tolia NH, Enemark EJ, Sim BK, Joshua-Tor L (2005) Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Cell 122:183–193

    Article  PubMed  CAS  Google Scholar 

  • Valkiūnas G, Iezhova TA, Loiseau C, Smith TB, Sehgal RN (2009) New malaria parasites of the subgenus Novyella in African rainforest birds, with remarks on their high prevalence, classification and diagnostics. Parasitol Res 104:1061–1077

    Article  PubMed  Google Scholar 

  • Vanriper C, Vanriper SG, Goff ML, Lair M (1986) The epizootiology and ecological significance of malaria in Hawaiian land birds. Ecological Monographs 56:327–344

    Article  Google Scholar 

  • Verra F, Chokejindachai W, Weedall GD, Polley SD, Mwangi TW, Marsh K, Conway DJ (2006a) Contrasting signatures of selection on the Plasmodium falciparum erythrocyte binding antigen gene family. Mol Biochem Parasitol 149:182–190

    Article  PubMed  CAS  Google Scholar 

  • Verra F, Polley SD, Thomas AW, Conway DJ (2006b) Comparative analysis of molecular variation in Plasmodium falciparum and P. reichenowi maebl gene. Parassitologia 48:567–572

    PubMed  CAS  Google Scholar 

  • Wertheimer SP, Barnwell JW (1989) Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69:340–350

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a National Institute of Health grant SC2AI089120-01A1 and the Bridge to the Doctorate grant #2R25-GM048972-11. We thank Dr. Ute Frevert and Steve Sullivan (New York University) for the P. gallinaceum samples and assistance with bioinformatics data. We also thank Shiho Kawamura for initial work on the project and Claire Loiseau for her guidance and for stimulating discussions.

Author information

Authors and Affiliations

  1. Department of Biology, San Francisco State University, San Francisco, CA, 94132, USA

    Criseyda Martinez, Timothy Marzec, Christopher D. Smith & Ravinder N. M. Sehgal

  2. Department of Medicine and Epidemiology, University of California at Davis, Davis, CA, 95616, USA

    Lisa A. Tell

Authors
  1. Criseyda Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy Marzec
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher D. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lisa A. Tell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ravinder N. M. Sehgal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravinder N. M. Sehgal.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 137 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinez, C., Marzec, T., Smith, C.D. et al. Identification and expression of maebl, an erythrocyte-binding gene, in Plasmodium gallinaceum . Parasitol Res 112, 945–954 (2013). https://doi.org/10.1007/s00436-012-3211-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-012-3211-4

Keywords

Search

Navigation