Exocytosis and protein secretion in Trypanosoma

Anne Geiger (1) , Christophe Hirtz (2, 3) , Thierry Becue (4) , Eric Bellard (4) , Delphine D. Centeno (5) , Daniel Gargani (6) , Michel Rossignol (4) , Gérard Cuny (1) , Jean-Benoît Peltier (4)

1 UMR INTERTRYP - Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides
2 Institute of Research in Biotherapy, Laboratory of Biochemistry and Clinical Proteomics
3 UM - Université de Montpellier
4 PROTEOMIQUE - Unité de Recherche Protéomique
5 UNH - Unité de Nutrition Humaine
6 UMR BGPI - Biologie et Génétique des Interactions Plante-Parasite

Background: Human African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins. Results: Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket. Conclusions: This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing Trypanosoma to exchange proteins at least between parasites and/or to manipulate the host immune system.

Mots clés: TRYPANOSOME

Mots clés: RELATION HOTE-PARASITE

Domaines: Parasitologie

Anne Geiger, Christophe Hirtz, Thierry Becue, Eric Bellard, Delphine D. Centeno, et al.. Exocytosis and protein secretion in Trypanosoma. BMC Microbiology, 2010, 10, pp.20. ⟨10.1186/1471-2180-10-20⟩. ⟨hal-02502942⟩