91 Global Analysis of Glycosylphosphatidylinositols or GPIomics of Infective Trypomastigote Forms of Trypanosoma Cruzi

Wednesday, November 4, 2009: 12:00 PM
Kohlberg (Camino Real Hotel)
Ernesto S. Nakayasu , Dept. of Biological Sciences, The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX
Alexandre F. Marques , Dept. of Biological Sciences, The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX
Felipe G. Lopes , Dept. of Biological Sciences, The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX
Igor C. Almeida , Dept. of Biological Sciences, The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX
Glycosylphosphatidylinositol (GPI)-anchoring is a ubiquitous post-translational modification of proteins of eukaryotes. In mammals, GPI is essential for embryonic development, and GPI-anchored proteins (GPI-APs) participate in relevant biological processes such as cell-cell interactions and antigenic presentation. In lower eukaryotes (e.g., protozoa, fungi), GPI-anchored molecules are implicated in key host-pathogen interactions such as host-cell adhesion and invasion, and pathogenesis. Recently, we have described a highly sensitive and straightforward approach that employs liquid chromatography-tandem mass spectrometry (LC-MSn) for the analysis of the GPIome (GPIomics) of non-infective epimastigote forms of Trypanosoma cruzi, the etiologic agent of Chagas disease (Nakayasu et al., Mol. Syst. Biol., 2009). Here we use the GPIomic approach to analyze GPIs (from GPI-APs and free GPIs) of the infective T. cruzi trypomastigote forms derived from parasite-infected mammalian cells. We have identified approximately 100 GPI species, most of them previously unknown. In contrast to epimastigote-derived GPIs, trypomastigote-derived GPIs have longer glycan core and sn-1-O-alkyl-2-O-acyl-glycerolipid moiety frequently containing unsaturated fatty acid chains (C18:1 or C18:2). Also, several lyso-alkyl GPIs, not found in epimastigotes, were observed in trypomastigotes. These traits underline significant differences in the GPI biosynthesis between epimastigote and trypomastigote forms that could be exploited for the development of new and more effective therapeutic approaches for Chagas disease. Acknowledgments: NIH grants R01AI070655 and 5G12RR008124, and NIH/RISE/UTEP program.