Interaction between Trypanosoma cruzi and host cell: study of FLY domain, a conserved carboxil-subterminal motiv of gp85/trans-sialidases.

Author(s)

Melissa Regina Fessel

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2006-11-24

Examining board members

Maria Júlia Manso Alves; Roger Chammas; Ronaldo Bento Quaggio; Sergio Schenkman; Shirley Schreier

• Advisor: Maria Júlia Manso Alves

Abstract

Trypanosoma cruzi the causative agent of Chagas´ disease is an obligatory intracellular parasite in the mammalian host. Altrough the mechanism of trypomastigotes invasion of host cells has been intensively studied, a final and integrate picture of the process remains elusive. Members of the gp85/trans-sialidase superfamily have been implicated in the parasite-host interaction, with Tc85 family (85 kDa glycoproteins) implicated in the adhesion step. Our laboratory showed that Tc85-11, one member of Tc85 family, is a multi-adhesive molecule, with binding sites located at the amino- and carboxi-portions of the protein. The conserved \"FLY domain\" (peptide J) is present in all members of the family, binds to cytokeratin 18 (CK18) and enhances T. cruzi invasion (Magdesian et al., 2001). Herein, we localized the binding site of \"FLY domain\" on the amino-portion of CK18 and demonstrated an increase of trypomastigotes adhesion to extracellular matrix upon FLY treatment. The \"FLY domain\" can modulate T. cruzi infection in vitro and apparently is responsible for inducing the secretion of molecules by the host that inhibit trypomastigote invasion. (AU)