Plasmodium and Toxoplasma: membrane biogenesis and host cell – parasite interactions

Team leaders :
BRAUN-BRETON Catherine (Professeur UM)
LEBRUN Maryse (DR INSERM)
 

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 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 - Equipe FRM - Lebrun team   
log frmOur research aims at deciphering the molecular mechanisms of cell invasion by 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 secondary endosymbisosis of a red algae that homes numerous essential cellular functions.

 

The Biology of lipids in Apicomplexan parasites and pharmacological applications
Our research is dedicated to membrane biogenesis and lipid metabolism that are major and essential for the differentiation and development of Apicomplexa parasites Plasmodium and Toxoplasma in their host. More recently our interest also extended to the analysis of phosphoinositides and their function in Plasmodium biology.

 

Host cell remodelling by Plasmodium falciparum
Our research focuses on P. falciparum-induced changes of its host erythrocyte. 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

 


 

- 2017 Publications -
 

-Wein S, Taudon N, Maynadier M, Tran Van Ba C, Margout D, Bordat Y, Fraisse L, Wengelnik K, Cerdan R, Bressolle-Gomeni F, Vial HJ. High Accumulation and In Vivo Recycling of the New Antimalarial Albitiazolium Lead to Rapid Parasite Death. Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00352-17. doi: 10.1128/AAC.00352-17.

-Francisco Hilario F, Traoré M, Zwick V, Berry L, Simões-Pires C, Cuendet M, Fantozzi N, Pereira de Freitas R, Maynadier  M, Wein S, Vial H, Wong, YS. Synthesis of an uncharged tetra-cyclopeptide acting as transmembrane carrier: enhanced cellular and nuclear uptake. Organic Letters, 2017, 19(3):612-615.

-Traoré M. D. M.,  Zwick V.,  Simões-Pires C. A., Nurisso A. ,  Issa M.,  Cuendet M., Maynadier M. , Wein S. , Vial H. , Jamet  H. and  Wong Y-S. Hydroxyl Ketone-Based Histone Deacetylase Inhibitors To Gain Insight into Class I HDAC Selectivity versus That of HDAC6. ACS Omega, 2017, 2 (4), pp 1550–1562 , DOI: 10.1021/acsomega.6b00481

- 2016 Publications -
 

Nguyen HM, El Hajj H, El Hajj R, Tawil N, Berry L, Lebrun M, Bordat Y, Besteiro S.
Toxoplasma gondii autophagy-related protein ATG9 is crucial for the survival of parasites in their host.
Cell Microbiol. 2016 Dec 19.

Berry L, Chen CT, Reininger L, Carvalho TG, El Hajj H, Morlon-Guyot J, Bordat Y, Lebrun M, Gubbels MJ, Doerig C, Daher W.
The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence.
Cell Microbiol. 2016 Aug;18(8):1106-20.

Lévêque MF, Nguyen HM, Besteiro S.
Repurposing of conserved autophagy-related protein ATG8 in a divergent eukaryote.
Commun Integr Biol. 2016 Jul 1;9(4):e1197447.

Lévêque MF, Berry L, Besteiro S.
An evolutionarily conserved SSNA1/DIP13 homologue is a component of both basal and apical complexes of Toxoplasma gondii.
Sci Rep. 2016 Jun 21;6:27809.

Daher W, Morlon-Guyot J, Alayi TD, Tomavo S, Wengelnik K, Lebrun M.
Identification of Toxoplasma TgPH1, a pleckstrin homology domain-containing protein that binds to the phosphoinositide PI(3,5)P2.
Mol Biochem Parasitol. 2016 May;207(1):39-44.


Braun-Breton C, Abkarian M.

Red Blood Cell Spectrin Skeleton in the Spotlight.
Trends Parasitol. 2016 Feb;32(2):90-2.


Parker ML, Penarete-Vargas DM, Hamilton PT, Guérin A, Dubey JP, Perlman SJ, Spano F, Lebrun M, Boulanger MJ.

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair.
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):398-403.


Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ; Abdelmohsen K; Abe A; Abedin MJ; Abeliovich H et al.
Publisher: Taylor & Francis, ISSN: 1554-8635 , Linking ISSN: 15548627 NLM ISO 



- 2015 Publications -

De Macêdo JP., Schumann Burkard G., Niemann M., Barrett MP., Vial H., Mäser P., Roditi I., Schneider A., Bütikofer P.(2015) An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei. PLoS Pathog. May 6;11(5):e1004875. doi: 10.1371/journal.ppat.1004875. eCollection.

Contet A., Pihan E., Lavigne M., Wengelnik K., Maheshwari S., Vial H., Douguet D. & Cerdan R. (2015) Plasmodium falciparum CTP:phosphocholine cytidylyltransferase possesses two functional catalytic domains and is inhibited by a CDP-choline analog selected from a virtual screening., FEBS Letter, Apr 13; 589(9):992-1000. doi: 10.1016/j.febslet.2015.03.003. Epub 2015 Mar 13. PMID: 25771858

Winkler M., Maynadier M., Wein S., Lespinasse MA., Boumis G., Miele AE., Vial H., Wong YS. (2015). Uncovering new structural insights for antimalarial activity from cost-effective aculeatin-like derivatives. Org Biomol Chem. 2015, 13(7):2064-77. doi: 10.1039/c4ob02459a. PMID: 25519040.

Mbengue A., Vialla E., Berry L., Fall G., Audiger N., Demettre-Verceil E, Boteller D., Braun-Breton C.  (2015) New export pathway in Plasmodium falciparum-infected erythrocytes: role of the parasite group II chaperonin, PfTRiC. Traffic - 16(5):461-475

Besteiro S., Blanc-Potard A., Bonazzi M., Briant L., Chazal N., Cornillot E., Lentini G., Matkovic R., Sanosyan A., Tuaillon E., Van de Perre P.  (2014) Montpellier Infectious Diseases - Pôle Rabelais (MID) 3rd annual meeting. Infect Genet Evol. 2015 Jun;32:161-4.

Besteiro S. (2015) Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you. Microb Cell. 2(6): 178-181

Pihan E., Delgadillo RF., Tonkin ML., Pugnière M., Lebrun M., Boulanger MJ., Douguet D. (2015) Computational and biophysical approaches to protein-protein interaction inhibition of Plasmodium falciparum AMA1/RON2 complex. J Comput Aided Mol Des.

Debaisieux S., Lachambre S., Gross A., Mettling C., Besteiro S., Yezid H., Henaff D., Chopard C., Mesnard JM., Beaumelle B. (2015) HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup. Nat Commun.  4;6:6211

Rugarabamu G., Marq JB., Guérin A., Lebrun M., Soldati-Favre D. (2015) Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to micronemal protein protease 1 activity during invasion. Mol Microbiol. Apr 2.

Lentini G., Kong-Hap M., El Hajj H., Francia M., Claudet C., Striepen B., Dubremetz JF., Lebrun M.  (2015) Identification and characterization of Toxoplasma SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite. Cell Microbiol. 17(1):62-78.

Morlon-Guyot J., Pastore S., Berry L., Lebrun M., Daher W.  (2015) Toxoplasma gondii Vps11, a subunit of HOPS and CORVET tethering complexes, is essential for the biogenesis of secretory organelles. Cellular Microbiology, 1157-1178.

Daher W., Morlon-Guyot J., Sheiner L., Lentini G., Berry L., Tawk L., Dubremetz JF., Wengelnik K., Striepen B., Lebrun M. (2015) Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii. Cellular Microbiology, 559-578.

Lévêque M., Berry L., Cipriano M., Nguyen Hoa-Mai., Striepen B., Besteiro S. (2015) Autophagy-related protein ATG8 has a non-canonical function for apicoplast inheritance in Toxoplasma gondii. Mbio, In press.

Risco-Castillo V., Topçu Selma., Marinach C., Manzon G., Bigorgne A.E., Briquet S., Baudin X., Lebrun M., Dubremetz J.F., and Olivier Silvie.  (2015) Malaria Sporozoites Traverse Host Cells within Transient Vacuoles.  Cell Host & Microbes. In press

- 2014 Publications -


Penarete-Vargas DM., Boisson A., Urbach S., Chantelauze H., Peyrottes S., Fraisse L., Vial HJ. (2014) A Chemical Proteomics Approach for the Search of Pharmacological Targets of the Antimalarial Clinical Candidate Albitiazolium in Plasmodium falciparum Using Photocrosslinking and Click Chemistry. PLoS One, 9(12):e113918. doi: 10.1371.

Nagy GN., Marton L., Contet A., Ozohanics O., Ardelean LM., Révész A., K Vékey K., Irimie FD.,  Vial H., Cerdan R., Vertessy BG. (2014) Composite aromatic box: a structural motif for binding and enzyme-catalyzed conversion of quaternary ammonium substrates, Angew Chem Int Ed Engl. 53(49):13471-6. doi: 10.1002/anie.201408246; PMID: 25283789

Vial H., and Wengelnik K. (2014) Phospholipid metabolism, Encyclopedia of Malaria, (M Hommel and PG Kremsner Edit),  Springer Press

Vial H.J., and Wengelnik K. (2014). Phospholipid metabolism. In Encyclopedia of Malaria, edited by Marcel Hommel and Peter G. Kremser, Springer. Electronic and printed version expected in 2017.

Wein S., Tran Van Ba C., Maynadier M., Y. Bordat., Perez J., Peyrottes S., Fraisse L. & Vial HJ. (2014) New insight in the mechanism of accumulation and intraerythrocytic compartmentation of albitiazolium - a new type of antimalarial. Antimicrobial Agents and Chemotherapy, 58(9), 5519-5527.

Ruiz J., Azémaa J., Payrastre C., Baltas M., Tuccio B., Vial H., André-Barrès C. (2014)  Antimalarial bicyclic peroxides belonging to the G-factor family: mechanistic aspects of their formation and iron (II) induced reduction, Current Topics in Medicinal Chemistry, 14(14):1668-1683; PMID: 25116578, ISSN: 1568-0266

Peyrotte S., Caldarelli S., Wein S., Périgaud C., and Vial H. (2014) Exploring prodrug approaches for Albitiazolium and its analogues, Current Topics in Medicinal Chemistry ;14(14):1653-1667; PMID: 25116583, ISSN: 1568-0266

Ruiz J., Mallet-Ladeira S., Maynadier M., Vial H. and André-Barrès C. (2014) Design, synthesis and evaluation of new tricyclic endoperoxides as potential antiplasmodial agents. Org Biomol Chem. 12(28):5212-21

Saidani N., Botte C., Deligny M., Bonneau AL., Reader J., LasselinR., Merer G., Niepceron A.,  Brossier F., Cintrat J.C., Rousseau B., Birkholtz LM., Cesbron-Delauw MF., Dubremetz JF., Mercier C., Vial H., Lopez R., and Marechal E. (2014) Discovery of compounds blocking the proliferation of Toxoplasma gondii and Plasmodium falciparum in a chemical space based on piperidinyl-benzimidazolidinone analogs, Antimicrob. Agents Chemother 58(5):2586. DOI: 10.1128/AAC.01445-13, PMID: 24550329

Degardin M., Wein S., Duckert JF., Maynadier M., Guy A., Durand T., R Escale R., Vial H. and Vo-Hoang Y.  (2014)Development of the first oral bioprecursors of bis-alkylguanidine antimalarial drugs., ChemMedChem.  9:300-4. doi: 10.1002/cmdc.201300419; PMID: 24403182.

Lamarque MH., Roques M., Kong-Hap M., Tonkin ML., Rugarabamu G., Marq JB., Penarete-Vargas DM., Boulanger MJ., Soldati-Favre D., Lebrun M.  (2014) Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites. Nat Commun.  Jun 17;5:4098.

Morlon-Guyot J., Berry L., Chen CT., Gubbels MJ., Lebrun M., Daher W. (2014) The Toxoplasma gondii calcium-dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cell Microbiol. 95-114.

Salamun J., Kallio J., Daher W., Soldati-Favre D., and Kursula I. (2014) Structure of Toxoplasma gondii coronin: an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress. FASEB Journal, 4729-4747.

Nguyen-Chi M., Phan QT., Gonzalez C., Dubremetz JF., Levraud JP., Lutfalla G. (2014) Transient infection of the zebrafish notochord with E. coli induces chronic inflammation. Dis Model Mech.  Jul;7(7):871-82.

Bernut A., Herrmann JL., Kissa K., Dubremetz JF., Gaillard JL., Lutfalla G., Kremer L.  (2014) Proc Natl Acad Sci U S A. Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation.  Mar 11;111(10)

Saïdani N., Botté CY., Deligny M., Bonneau AL., Reader J., Lasselin R., Merer G., Niepceron A., Brossier F., Cintrat JC., Rousseau B., Birkholtz LM., Cesbron-Delauw MF., Dubremetz JF., Mercier C., Vial H., Lopez R., Maréchal E.  (2014) Discovery of compounds blocking the proliferation of Toxoplasma gondii and Plasmodium falciparum in a chemical space based on piperidinyl-benzimidazolone analogs. Antimicrob Agents Chemother.  May;58(5):2586-97.

Niehus S., Smith TK., Azzouz N., Campos MA., Dubremetz JF., Gazzinelli RT., Schwarz RT., Debierre-Grockiego F.  (2014) Virulent and avirulent strains of Toxoplasma gondii which differ in their glycosylphosphatidylinositol content induce similar biological functions in macrophages. PLoS One.  Jan 28;9(1):e85386.

Fond G., Macgregor A., Tamouza R., Hamdani N., Meary A., Leboyer M., Dubremetz JF.  (2014) Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate. Eur Arch Psychiatry Clin Neurosci.  Mar;264(2):179-83.

- 2013 Publications -


Vial H., Taramelli D., Boulton IC., Ward SA., Doerig C. and Chibale K., (2013), CRIMALDDI: platform technologies and novel anti-malarial drug targets, Malaria Journal, 12:396, doi: 10.1186/1475-2875-12-396, PMID: 24498961

Sen P., Vial HJ., Radulescu O. (2013) Kinetic modelling of Phospholipid synthesis in Plasmodium knowlesi unravels crucial steps and relative importance of multiple pathways., BMC Systems Biology, 7(1):123. doi: 10.1186/1752-0509-7-123. PMID: 24209716.

De Macêdo JP., Schmidt R., Sigel E., Rentsch D., Vial H.J.,  Mäser P. and Peter Bütikofer. (2013) Characterization of choline uptake in Trypanosoma brucei procyclic and bloodstream forms ; Mol Biochem. Parasit. 90, 16-22 (IF : 2.73)

Pasini E., Van den Ierssel D., Vial HJ and Kocken CMH, A novel live-dead staining methodology to study malaria parasite viability, Malaria J, 12:190. doi: 10.1186/1475-2875-12-190 ; PMID: 23758788 (IF : 3.19)

Ruiz J., Tuccio B., Lauricella R., Maynadier M., Vial H., André-Barrès C. (2013) Synthesis and antiplasmodial evaluation of cyclopropyl analogs of the G-factor bicyclic peroxide. Tetrahedron, 69, 6709-6720, (IF : 3.22)

Nagy G., Marton L., Krámos B., Oláh J., Revész A., Véky K., Delsuc F., Hunyadi-Gulyas E., Medzihradszky K., Lavigne L., Vial H., Cerdan R., Vertessy B. (2013) Evolutionary and mechanistic insights into substrate and product accommodation of CTP:phosphocholine cytidylyltransferase from Plasmodium falciparum. FEBS J. 2013, 280(13):3132-48 (IF :3.04). doi: 10.1111/febs.12282., PMID: 23578277

Traoré M., Mietton F., Maubon D.,  Peuchmaur M.,  Francisco HF., Pereira de Freitas R., Bougdour A., Curt A.,  Maynadier M., Vial H., Pelloux H., Hakimi MA., Wong YS.  (2013) Flexible
synthesis and evaluation of diverse anti-Apicomplexa cyclic peptides. J. Organic Chemistry,78, 3655-75. (IF : 4.22)

Lombard MC., N Da DD., Tran Van Ba C., Wein S., Norman J., Wiesner L., Vial H.  (2013) Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids. Malar J. 12:71. doi: 10.1186/1475-2875-12-71. PMID:  23433124, (IF : 3.19)

Caldarelli S., El Fangour S., Wein S., C. Tran van  Ba., Perigaud C., Pellet A., Vial H.,  Peyrottes S. ( 2013) New Bis-Thiazolium Analogues as Potential Anti-Malarial Agents: Design, Synthesis and Biological Evaluation, J Med Chem. 56(2):496-509; doi: 10.1021/jm3014585, PMID: 23289711(IF : 5,25)

Maheshwari S.,  Lavigne M., Alberge B., Pihan E., Kocken C., Wengelnik K., Douguet D.,  Vial H. And Cerdan R. (2013) Functional characterization of Plasmodium falciparum CTP:phosphoethanolamine cytidylyltransferase, the rate-limiting step of the de novo phosphatidylethanolamine biosynthesis pathway. Biochem J., 450(1):159-67. doi: 10.1042/BJ20121480; PMID: 23198904 , (IF : 4.9)

Mbengue A., Audiger N., Vialla E., Dubremetz JF., Braun-Breton C.  (2013) Novel Plasmodium falciparum Maurer's clefts protein families implicated in the release of infectious merozoites. Mol Microbiol. 88(2): 425-42.

Kemp LE., Rusch M., Adibekian A., Bullen HE., Graindorge A., Freymond C., Rottmann M., Braun-Breton C., Baumeister S., Porfetye AT., Vetter IR., Hedberg C., Soldati-Favre D. (2013). Characterization of a serine hydrolase targeted by acyl-protein thioesterase inhibitors in Toxoplasma gondii. J Biol Chem. 288(38):27002-18.

Yam XY., Birago C., Fratini F., Di Girolamo F., Raggi C., Sargiacomo M., Bachi A., Berry L., Fall G., Curra C., Pizzi E., Braun-Breton C., Ponzi M. (2013). Proteomic analysis of detergent-resistant membrane micro-domains in trophozoite blood stage of the human malaria parasite Plasmodium falciparum. Mol Cell Proteomics 12(12):3948-61

Kong-Hap MA., Mouammine A., Daher W., Berry L., Lebrun M., Dubremetz JF., Besteiro S.  (2013) Regulation of ATG8 membrane association by ATG4 in the parasitic protist Toxoplasma gondii. Autophagy. September ;9(9):1334-48

Tonkin ML., Crawford J., Lebrun ML., Boulanger MJ. (2013)  Babesia divergens and Neospora caninum apical membrane antigen 1 structures reveal selectivity and plasticity in apicomplexan parasite host cell invasion. Protein Sci.  Jan;22(1):114-27

De Napoli. M.G., N. de Miguel., Lebrun M., Moreno S.N.J., Angel S.O., Corvi M.M.  (2013) N-terminal palmitoylation is required for Toxoplasma gondii HSP20 inner membrane complex localization. 2013 Biochimica and Biophysica Acta (BBA) - Molecular Cell Research. Jun;1833(6):1329-37.

Vanagas L., Dalmasso MC., Dubremetz JF., Portiansky EL., Olins DE., Angel SO. (2013) Parasitology. Epichromatin is conserved in Toxoplasma gondii and labels the exterior parasite chromatin throughout the cell cycle. Aug;140(9):1104-10.

Mueller C., Klages N., Jacot D., Santos JM., Cabrera A., Gilberger TW., Dubremetz JF., Soldati-Favre D. (2013) The Toxoplasma protein ARO mediates the apical positioning of rhoptry organelles, a prerequisite for host cell invasion. Cell Host Microbe. Mar 13;13(3):289-301.

Azzouz N., Kamena F., Laurino P., Kikkeri R., Mercier C., Cesbron-Delauw MF., Dubremetz JF., De Cola L., Seeberger PH. (2013) Toxoplasma gondii secretory proteins bind to sulfated heparin structures. Glycobiology. Jan;23(1):106-20.

Jacot D., Daher W., Soldati-Favre D. (2013) Toxoplasma gondii myosin F, an essential motor for centrosomes positioning and apicoplast inheritance. EMBO Journal, 1702-1716.