Trypanosoma cruzi: parasite-host cell interaction

• Grant number: 99/12459-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2000
• End date: September 30, 2004
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria Julia Manso Alves
• Grantee: Maria Julia Manso Alves
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Walter Colli
• Associated scholarship(s): 00/11060-4 - Interactions between Trypanosoma cruzi and the vertebrate host cell, BP.PD; 00/08121-1 - Comparative study of glucose and proline transport in Trypanosoma cruzi different stages of differentiation, BP.PD

Abstract

Trypanosoma cruzi, the ethiologic agent of Chagas' disease, is an obligatory intracellular parasite having three main developing stages: the infective form, the trypomastigote and the reproductive forms, the epimastigote and the amastigote. In order to reach and enter host cells the trypomastigotes must cross the endothelial barrier of the vertebrate host and thus must interact, at least, with two structures namely, the basal membrane and the plasma membrane, in addition to other elements of the extraceilular matrix. On the host cell side, several molecules have been suggested to intermediate this process, as fibronectin, sialic acid, collagen, heparan sulfate, integrins and laminin. Our laboratory, for the first time in the literature, has shown that a small group of molecules belonging to the Tc-85glycoprotein family binds to laminin. On the parasite side, several surface proteins or glycoproteins have also been related with the adhesion and invasion processes, especially those having molecular mass between 85-90 kDa, including an 85 kDa protein that binds to fibronectin and collagen, possibly related to theTe-85 family, and a 65 kDa protein that binds to heparan sulfate. Recently, our laboratory cloned and expressed the fusion protein of one member of the Tc-85 family that binds to laminin (Tc85-11), as well as peptides which correspond to different regions of the molecule. Preliminary studies suggested that in addition to sites for laminin binding there are other adhesion sites to the plasma membrane of the host cell, suggesting multiple binding sites in the glycoprotein, as it is common to molecules of the kind. We find it very important for the understanding of the parasite adhesion mechanism to determine the binding region of the molecule responsible for the attachment to cells, as well as the identification of the receptor on the host cell membrane. Data in the literature, however, point out to the involvement of other members of that group of molecules or unrelated molecules, making it necessary to identify, isolate and characterize other surface proteins of the parasite responsible for adhesion and invasion. With that objectives in mind the problem will be approached using different strategies: Mapping on Tc85-11 the aminoacids involved in binding to laminin and other molecules on the host cell surface membrane- Isolate other parasite adhesion molecules and their respective receptors... (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

L.C. MILETTI; M. ALMEIDA-DE-FARIA; W. COLLI; M.J.M. ALVES. Immunocytochemical and biochemical detection of alpha-L-fucosidase in Trypanosoma cruzi. Brazilian Journal of Medical and Biological Research, v. 36, n. 5, p. 595-603, 2003-05-00. (99/12459-9)

H. ULRICH; M.J.M. ALVES; W. COLLI. RNA and DNA aptamers as potential tools to prevent cell adhesion in disease. Brazilian Journal of Medical and Biological Research, v. 34, n. 3, p. 295-300, 2001-03-00. (99/12459-9)

OLIVEIRA‚ M.F.; BIJOVSKY‚ A.T.; CARVALHO‚ T.U.; SOUZA‚ W.; ALVES‚ M.M.; COLLI‚ W.. A monoclonal antibody to Trypanosoma cruzi trypomastigotes recognizes a myosin tail epitope. Parasitology Research, v. 87, n. 12, p. 1043-1049, 2001. (99/12459-9)

SILBER, ARIEL M.; TONELLI, RENATA R.; MARTINELLI, MARCELA; COLLI, WALTER; ALVES, MARIA JÚLIA M.. Active transport of L-proline in Trypanosoma cruzi. Journal of Eukaryotic Microbiology, v. 49, n. 6, p. 441-446, Nov. 2002. (99/12459-9)

MARROQUIN-QUELOPANA, MIRYAM; OYAMA JÚNIOR, SERGIO; PERTINHEZ, THELMA AGUIAR; SPISNI, ALBERTO; JULIANO, MARIA APARECIDA; JULIANO, LUIZ; COLLI, WALTER; ALVES, MARIA JÚLIA M.. Modeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site. Biochemical and Biophysical Research Communications, v. 325, n. 2, p. 612-618, Dec. 2004. (99/12459-9)

ULRICH, HENNING; MAGDESIAN, MARGARET H.; ALVES, MARIA JÚLIA M.; COLLI, WALTER. In vitro selection of RNA aptamers that bind to cell adhesion receptors of Trypanosoma cruzi and inhibit cell invasion. Journal of Biological Chemistry, v. 277, n. 23, p. 20756-20762, June 2002. (99/12459-9)