Membrane biogenesis and interactions with the host cell in Plasmodium and Toxoplasma

  Catherine BRAUN-BRETON and Maryse LEBRUN

 LPHI - UMR 5235

 Place Eugène Bataillon, 34095 Montpellier

    Phone: +33 4 67 14 37 42, +33 4 67 14 34 55

    Email : cbb@univ-montp2.fr    maryse.lebrun@univ-montp2.fr

 Website

Activities are mainly focused on cell and molecular biology issues of two Apicomplexa parasites, Plasmodium falciparum (Malaria) and Toxoplasma gondii (Toxoplasmosis). They have developed a number of fascinating cell biological processes, in response to their parasitic life style. The objectives are to clarify the main processes that could be major and/or are essential for the differentiation and development of these parasites in their host cells and to determine original features in term of biological processes versus mammalian cells for example.

Our research is organised around the 3 following axes:

Host cell invasion and intracellular survival in Apicomplexan parasites

Maryse Lebrun

Our research aims at deciphering the molecular mechanisms of invasion in Toxoplasma gondii that has been conserved across the phylum during evolution. Our activities are also focused on autophagy and on vesicular trafficking to the apicoplast, a plastid acquired from endosymbisosis secondary of a red algae that home numerous essential cellular functions.

The Biology of lipids in Apicomplexan parasites and pharmacological applications

Catherine Braun Breton

Our research focuses on P. falciparum-induced changes of its host erythrocytes. Our main objectives are to decipher the roles of Maurer's clefts, a membrane compartment transposed by the parasite at the periphery of its host cell and to characterize the parasite-induced changes of the erythrocyte membrane and cytoskeleton crucial for parasite entry into and egress from the red blood cell.

Keywords: Malaria, Toxoplasmosis, Molecular and Cell Biology, Pharmacology

Main publications

• Tonkin*, Roques*, Lamarque, Pugnignère, Douguet, Crawford, Lebrun*, Boulanger* (2011) Host cell invasion by Apicomplexan parasites: Insights from the structure of AMA1 in complex with a RON2 peptide. Science, 333(6041):463-7., *equal contribution.
• Raabe, A. C., Wengelnik, K., Billker, O. and Vial, H. J. (2011) Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation. Cell. Microbiol., 13(7):955-66.
• Abkarian, M., Massiera, G., Berry, L., Roques, M. and Braun-Breton, C. (2011). A novel mechanism for egress of malarial parasite from red blood cells. Blood 117(15):4118-24
• Besteiro S, Brooks CF, Striepen B, Dubremetz JF. (2011) Autophagy Protein Atg3 is Essential for Maintaining Mitochondrial Integrity and for Normal Intracellular Development of Toxoplasma gondii Tachyzoites. PLoS Pathog. 7(12):e100241
• Lamarque, Besteiro, Papoin, Roques, Vulliez-Le Normand, Morlon-Guyot, Dubremetz, Fauquenoy, Tomavo, Faber, Kocken, Thomas, Boulanger, Bentley, and M. Lebrun. (2011). The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by Apicomplexan parasites. Plos Pathog. 0;7(2):e1001276.
• Tawk, L., J. F. Dubremetz, P. Montcourrier, G. Chicanne, F. Merezegue, V. Richard, B. Payrastre, M. Meissner, H. J. Vial, C. Roy, K. Wengelnik, and M. Lebrun (2011). Phosphatidylinositol 3-monophosphate is involved in Toxoplasma apicoplast biogenesis. PLoS Pathog 7(2): e1001286.
• Calas M., Ancelin ML., Piquet, Escale R., Ouattara M., and Vial H. (2007) Potent antimalarial activity of 2-aminopyridinium salts, amidines and guanidines. J. Med Chem.: 50, 6307-15,
• Blisnick, T., Vincensini, L., Fall, G. and Braun Breton, C. (2006). PP1 phosphatase, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites. Cell. Microbiol. 8: 591 – 601
• Cérède O, J. F. Dubremetz, M. Soête, D. Deslée, H. Vial, D. Bout, M. Lebrun (2005). Synergistic role of micronemal proteins in Toxoplasma gondii virulence. J. Exp. Med. 201:453-463.
• Vial H., Wein S, Farenc C, Bressolle F, Kocken C, Thomas A., Calas M. (2004) Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl. Acad. Sci. USA, 101: 15458- 15463
• Wengelnik K., Vidal V., Ancelin ML, Cathiard AM, Morgat JL, Kocken C., Calas M., Herrera, S. Thomas, A. and Vial, H. (2002) A class of potent antimalarials and their specific accumulation in infected erythrocytes, Science, 295: 1311-1314.