title: Bioinformatics and functional analysis of an Entamoeba histolytica mannosyltransferase necessary for parasite complement resistance and hepatical infection.
abstract: The glycosylphosphatidylinositol (GPI) moiety is one of the ways by which many cell surface proteins, such as Gal/GalNAc lectin and proteophosphoglycans (PPGs) attach to the surface of Entamoeba histolytica, the agent of human amoebiasis. It is believed that these GPI-anchored molecules are involved in parasite adhesion to cells, mucus and the extracellular matrix. We identified an E. histolytica homolog of PIG-M, which is a mannosyltransferase required for synthesis of GPI. The sequence and structural analysis led to the conclusion that EhPIG-M1 is composed of one signal peptide and 11 transmembrane domains with two large intra luminal loops, one of which contains the DXD motif, involved in the enzymatic catalysis and conserved in most glycosyltransferases. Expressing a fragment of the EhPIG-M1 encoding gene in antisense orientation generated parasite lines diminished in EhPIG-M1 levels; these lines displayed reduced GPI production, were highly sensitive to complement and were dramatically inhibited for amoebic abscess formation. The data suggest a role for GPI surface anchored molecules in the survival of E. histolytica during pathogenesis.
authors.affiliation: Institut Pasteur, Unité de Biologie Cellulaire du Parasitisme, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Samantha
authors.initials: S
authors.lastname: Blazquez
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marion
authors.forename: Christophe
authors.initials: C
authors.lastname: Ausseur
authors.forename: Divya
authors.initials: D
authors.lastname: Vats
authors.forename: Mickael
authors.initials: M
authors.lastname: Krzeminski
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rigothier
authors.forename: Rachid C
authors.initials: RC
authors.lastname: Maroun
authors.forename: Alok
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillén
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D019295:Computational Biology; D006224:Cricetinae; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000276:immunology / Q000472:pathogenicity; D004749:Entamoebiasis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008297:Male; D008364:Mannosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008647:Mesocricetus; D008958:Models, Molecular; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein
chemical_list: D017261:Glycosylphosphatidylinositols; D015800:Protozoan Proteins; D003165:Complement System Proteins; D008364:Mannosyltransferases