Factors involved in migration by gastric mucin and in cell invasion of Trypanosoma cruzi metacyclic forms

• Grant number: 12/51420-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2013
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Nobuko Yoshida
• Grantee: Cristian Andrés Cortez Plaza
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Oral infection by metacydic forms of Trypanosoma cruzi is currently the main mode of Chagas' disease transmission in Brasil. Parasites attach to the gastric mucin, traverse the mucus layer and invade the gastric epithelium, which is is the portal of entry to systemic infection. Adhesion to gastric mucin and cell invasion, crucial for the establishment of infection by the oral route, are mediated by the metacydic stage-specific surface molecule gp82. Little is known about parasite factors implicated in migration through the gastric mucin. As regards the host cell invasion by metacydic forms, some components of the signaling cascades of the host cell and the parasite were identified, but many more await to be revealed. The connections among the diverse elements of the signaling pathways, under different conditions, have also to be investigated. In this project we aim to: i) determine the involvement of mucinolytic enzymes in parasite migration through the gastric mucin layer and identify the refirered enzymes, ii) examine the mucinolytic activity of different T. cruzi strains and its association with the migration capacity, iii) investigate the participation of the kinases mTOR, PKC, PTK and PI3K in signaling pathways activated by different T. cruzi strains, iv) examine the involvement of diverse host cell kinases in metacydic form internalization under short term nutritional stress and determine the role of amino acids in modulating invasion. (AU)