Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Invasion of Erythrocytes


The development of an effective malaria vaccine is a world health priority and would be a critical step toward the control and eventual elimination of this disease. In addition, new pharmacological solutions are necessary as Plasmodium falciparum, the deadliest of the malaria-causing parasites, has developed resistance to every drug currently approved for treatment. Understanding the interactions required for the parasite to invade its erythrocyte host, as well as being valuable to our basic knowledge of parasite biology, is important for the development of drug-based therapies and vaccines. In this study we have, for the first time, filmed P. falciparum parasites invading erythrocytes while systematically blocking several specific interactions between the parasite and the erythrocyte. We have shown there is a sequential progression of specific interactions that occur in at least four distinct steps leading up to invasion. Previous vaccine attempts have targeted one or two of these steps, however, if a single vaccine were designed to block interactions at all four steps, the combined effect might so reduce invasion that parasite growth and disease progression would be arrested. A better understanding of each interaction during invasion, their role and order, can also inform the development of new anti-malarial drugs.


Vyšlo v časopise: Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Invasion of Erythrocytes. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004670
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004670

Souhrn

The development of an effective malaria vaccine is a world health priority and would be a critical step toward the control and eventual elimination of this disease. In addition, new pharmacological solutions are necessary as Plasmodium falciparum, the deadliest of the malaria-causing parasites, has developed resistance to every drug currently approved for treatment. Understanding the interactions required for the parasite to invade its erythrocyte host, as well as being valuable to our basic knowledge of parasite biology, is important for the development of drug-based therapies and vaccines. In this study we have, for the first time, filmed P. falciparum parasites invading erythrocytes while systematically blocking several specific interactions between the parasite and the erythrocyte. We have shown there is a sequential progression of specific interactions that occur in at least four distinct steps leading up to invasion. Previous vaccine attempts have targeted one or two of these steps, however, if a single vaccine were designed to block interactions at all four steps, the combined effect might so reduce invasion that parasite growth and disease progression would be arrested. A better understanding of each interaction during invasion, their role and order, can also inform the development of new anti-malarial drugs.


Zdroje

1. Bejon P, White MT, Olotu A, Bojang K, Lusingu JP, et al. (2013) Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data. Lancet Infect Dis 13: 319–327. doi: 10.1016/S1473-3099(13)70005-7 23454164

2. Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, et al. (2012) A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med 367: 2284–2295. doi: 10.1056/NEJMoa1208394 23136909

3. Cowman AF, Crabb BS (2006) Invasion of red blood cells by malaria parasites. Cell 124: 755–766. 16497586

4. Dvorak JA, Miller LH, Whitehouse WC, Shiroishi T (1975) Invasion of erythrocytes by malaria merozoites. Science 187: 748–750. 803712

5. Gilson PR, Crabb BS (2009) Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum merozoites. Int J Parasitol 39: 91–96. doi: 10.1016/j.ijpara.2008.09.007 18952091

6. Yahata K, Treeck M, Culleton R, Gilberger TW, Kaneko O (2012) Time-lapse imaging of red blood cell invasion by the rodent malaria parasite Plasmodium yoelii. PLoS One 7: e50780. doi: 10.1371/journal.pone.0050780 23227208

7. Crick AJ, Tiffert T, Shah SM, Kotar J, Lew VL, et al. (2013) An automated live imaging platform for studying merozoite egress-invasion in malaria cultures. Biophys J 104: 997–1005. doi: 10.1016/j.bpj.2013.01.018 23473482

8. Gilson PR, Nebl T, Vukcevic D, Moritz RL, Sargeant T, et al. (2006) Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum. Mol Cell Proteomics 5: 1286–1299. 16603573

9. Holder AA, Freeman RR (1984) The three major antigens on the surface of Plasmodium falciparum merozoites are derived from a single high molecular weight precursor. J Exp Med 160: 624–629. 6381636

10. McBride JS, Heidrich HG (1987) Fragments of the polymorphic Mr 185,000 glycoprotein from the surface of isolated Plasmodium falciparum merozoites form an antigenic complex. Mol Biochem Parasitol 23: 71–84. 2437453

11. Sanders PR, Cantin GT, Greenbaum DC, Gilson PR, Nebl T, et al. (2007) Identification of protein complexes in detergent-resistant membranes of Plasmodium falciparum schizonts. Mol Biochem Parasitol 154: 148–157. 17553576

12. Boyle MJ, Richards JS, Gilson PR, Chai W, Beeson JG (2009) Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites. Blood 115: 4559–4568. doi: 10.1182/blood-2009-09-243725 20220119

13. Harvey KL, Gilson PR, Crabb BS (2012) A model for the progression of receptor-ligand interactions during erythrocyte invasion by Plasmodium falciparum. Int J Parasitol 42: 567–573. doi: 10.1016/j.ijpara.2012.02.011 22710063

14. Tham WH, Healer J, Cowman AF (2012) Erythrocyte and reticulocyte binding-like proteins of Plasmodium falciparum. Trends Parasitol 28: 23–30. doi: 10.1016/j.pt.2011.10.002 22178537

15. Baum J, Chen L, Healer J, Lopaticki S, Boyle M, et al. (2009) Reticulocyte-binding protein homologue 5—an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol 39: 371–380. doi: 10.1016/j.ijpara.2008.10.006 19000690

16. Gao X, Gunalan K, Yap SS, Preiser PR (2013) Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum. Nat Commun 4: 2862. doi: 10.1038/ncomms3862 24280897

17. Singh S, More KR, Chitnis CE (2014) Role of calcineurin and actin dynamics in regulated secretion of microneme proteins in Plasmodium falciparum merozoites during erythrocyte invasion. Cell Microbiol 16: 50–63. doi: 10.1111/cmi.12177 23910910

18. Duraisingh MT, Triglia T, Ralph SA, Rayner JC, Barnwell JW, et al. (2003) Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes. Embo J 22: 1047–1057. 12606570

19. Stubbs J, Simpson KM, Triglia T, Plouffe D, Tonkin CJ, et al. (2005) Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes. Science 309: 1384–1387. 16123303

20. Tham WH, Wilson DW, Lopaticki S, Schmidt CQ, Tetteh-Quarcoo PB, et al. (2010) Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand. Proc Natl Acad Sci U S A 107: 17327–17332. doi: 10.1073/pnas.1008151107 20855594

21. Persson KE, McCallum FJ, Reiling L, Lister NA, Stubbs J, et al. (2008) Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. J Clin Invest 118: 342–351. 18064303

22. Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, et al. (2011) Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 480: 534–537. doi: 10.1038/nature10606 22080952

23. Wright KE, Hjerrild KA, Bartlett J, Douglas AD, Jin J, et al. (2014) Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. Nature 13715 [Epub ahead of print].

24. Chen L, Lopaticki S, Riglar DT, Dekiwadia C, Uboldi AD, et al. (2011) An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS Pathog 7: e1002199. doi: 10.1371/journal.ppat.1002199 21909261

25. Bustamante LY, Bartholdson SJ, Crosnier C, Campos MG, Wanaguru M, et al. (2013) A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants. Vaccine 31: 373–379. doi: 10.1016/j.vaccine.2012.10.106 23146673

26. Douglas AD, Williams AR, Knuepfer E, Illingworth JJ, Furze JM, et al. (2014) Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. J Immunol 192: 245–258. doi: 10.4049/jimmunol.1302045 24293631

27. Riglar DT, Richard D, Wilson DW, Boyle MJ, Dekiwadia C, et al. (2011) Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte. Cell Host Microbe 9: 9–20. doi: 10.1016/j.chom.2010.12.003 21238943

28. Besteiro S, Michelin A, Poncet J, Dubremetz JF, Lebrun M (2009) Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathog 5: e1000309. doi: 10.1371/journal.ppat.1000309 19247437

29. Tonkin ML, Roques M, Lamarque MH, Pugniere M, Douguet D, et al. (2011) Host cell invasion by apicomplexan parasites: insights from the co-structure of AMA1 with a RON2 peptide. Science 333: 463–467. doi: 10.1126/science.1204988 21778402

30. Cao J, Kaneko O, Thongkukiatkul A, Tachibana M, Otsuki H, et al. (2009) Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites. Parasitol Int 58: 29–35. doi: 10.1016/j.parint.2008.09.005 18952195

31. Collins CR, Withers-Martinez C, Hackett F, Blackman MJ (2009) An inhibitory antibody blocks interactions between components of the malarial invasion machinery. PLoS Pathog 5: e1000273. doi: 10.1371/journal.ppat.1000273 19165323

32. Richard D, MacRaild CA, Riglar DT, Chan JA, Foley M, et al. (2010) 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. J Biol Chem 285: 14815–14822. doi: 10.1074/jbc.M109.080770 20228060

33. Lamarque M, Besteiro S, Papoin J, Roques M, Vulliez-Le Normand B, et al. (2011) The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites. PLoS Pathog 7: e1001276. doi: 10.1371/journal.ppat.1001276 21347343

34. Harris KS, Casey JL, Coley AM, Karas JA, Sabo JK, et al. (2009) Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning. J Biol Chem 284: 9361–9371. doi: 10.1074/jbc.M808762200 19164290

35. Harris KS, Casey JL, Coley AM, Masciantonio R, Sabo JK, et al. (2005) Binding hot spot for invasion inhibitory molecules on Plasmodium falciparum apical membrane antigen 1. Infect Immun 73: 6981–6989. 16177378

36. Srinivasan P, Beatty WL, Diouf A, Herrera R, Ambroggio X, et al. (2011) Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion. Proc Natl Acad Sci U S A 108: 13275–13280. doi: 10.1073/pnas.1110303108 21788485

37. Treeck M, Zacherl S, Herrmann S, Cabrera A, Kono M, et al. (2009) Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process. PLoS Pathog 5: e1000322. doi: 10.1371/journal.ppat.1000322 19283086

38. Yap A, Azevedo MF, Gilson PR, Weiss GE, MT ON, et al. (2014) Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites. Cell Microbiol 16: 642–656. doi: 10.1111/cmi.12287 24571085

39. Tham WH, Schmidt CQ, Hauhart RE, Guariento M, Tetteh-Quarcoo PB, et al. (2011) Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes. Blood 118: 1923–1933. doi: 10.1182/blood-2011-03-341305 21685372

40. Leykauf K, Treeck M, Gilson PR, Nebl T, Braulke T, et al. (2010) Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite. PLoS Pathog 6: e1000941. doi: 10.1371/journal.ppat.1000941 20532217

41. Lew VL, Tiffert T (2007) Is invasion efficiency in malaria controlled by pre-invasion events? Trends Parasitol 23: 481–484. 17804296

42. Johnson JG, Epstein N, Shiroishi T, Miller LH (1980) Factors affecting the ability of isolated Plasmodium knowlesi merozoites to attach to and invade erythrocytes. Parasitology 80: 539–550. 6771738

43. McCallum-Deighton N, Holder AA (1992) The role of calcium in the invasion of human erythrocytes by Plasmodium falciparum. Mol Biochem Parasitol 50: 317–323. 1741019

44. Wasserman M, Chaparro J (1996) Intraerythrocytic calcium chelators inhibit the invasion of Plasmodium falciparum. Parasitol Res 82: 102–107. 8825202

45. Bartholdson SJ, Crosnier C, Bustamante LY, Rayner JC, Wright GJ (2013) Identifying novel Plasmodium falciparum erythrocyte invasion receptors using systematic extracellular protein interaction screens. Cell Microbiol 15: 1304–1312. doi: 10.1111/cmi.12151 23617720

46. Kobayashi K, Takano R, Takemae H, Sugi T, Ishiwa A, et al. (2013) Analyses of interactions between heparin and the apical surface proteins of Plasmodium falciparum. Sci Rep 3: 3178. doi: 10.1038/srep03178 24212193

47. Blackman MJ, Scott-Finnigan TJ, Shai S, Holder AA (1994) Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. J Exp Med 180: 389–393. 7516416

48. Lopaticki S, Maier AG, Thompson J, Wilson DW, Tham WH, et al. (2011) Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites. Infect Immun 79: 1107–1117. doi: 10.1128/IAI.01021-10 21149582

49. Bannister LH, Mitchell GH, Butcher GA, Dennis ED (1986) Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion. Parasitology 92 (Pt 2): 291–303. 2423944

50. Miller LH, Aikawa M, Johnson JG, Shiroishi T (1979) Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment and junction formation. J Exp Med 149: 172–184. 105074

51. Sheetz MP, Singer SJ (1974) Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions. Proc Natl Acad Sci U S A 71: 4457–4461. 4530994

52. Chen L, Xu Y, Healer J, Thompson JK, Smith BJ, et al. (2014) Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes. Elife 3: doi: 10.7554/eLife.04187

53. Howell SA, Well I, Fleck SL, Kettleborough C, Collins CR, et al. (2003) A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage. J Biol Chem 278: 23890–23898. 12686561

54. Barale JC, Blisnick T, Fujioka H, Alzari PM, Aikawa M, et al. (1999) Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1–42 maturase. Proc Natl Acad Sci U S A 96: 6445–6450. 10339607

55. Bargieri DY, Andenmatten N, Lagal V, Thiberge S, Whitelaw JA, et al. (2013) Apical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion. Nat Commun 4: 2552. doi: 10.1038/ncomms3552 24108241

56. O’Donnell RA, de Koning-Ward TF, Burt RA, Bockarie M, Reeder JC, et al. (2001) Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria. The Journal of experimental medicine 193: 1403–1412. 11413195

57. Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193: 673–675. 781840

58. Boyle MJ, Wilson DW, Richards JS, Riglar DT, Tetteh KK, et al. (2010) Isolation of viable Plasmodium falciparum merozoites to define erythrocyte invasion events and advance vaccine and drug development. Proc Natl Acad Sci U S A 107: 14378–14383. doi: 10.1073/pnas.1009198107 20660744

59. Azevedo M, Nie C, Elsworth B, Charnaud S, Sanders P, et al. (2014) Plasmodium falciparum transfected with ultra bright NanoLuc luciferase offers high sensitivity detection for the screening of growth and cellular trafficking inhibitors. PLoS One 9: e112571. doi: 10.1371/journal.pone.0112571 25392998

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa