Trypanosoma cruzi Binds to Cytokeratin through Conserved Peptide Motifs Found in the Laminin-G-Like Domain of the gp85/Trans-sialidase Proteins

Author(s)

Reis Teixeira, Andre Azevedo ^[1] ; Sardinha de Vasconcelos, Veronica de Cassia ^[1] ; Colli, Walter ^[1] ; Manso Alves, Maria Julia ^[1] ; Giordano, Ricardo Jose ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Biochem, Inst Chem, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 9, n. 9 SEP 2015.
• Web of Science Citations: 9

Abstract

Background Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is a disease that affects millions of people most of them living in South and Central Americas. There are few treatment options for individuals with Chagas' disease making it important to understand the molecular details of parasite infection, so novel therapeutic alternatives may be developed for these patients. Here, we investigate the interaction between host cell intermediate filament proteins and the T. cruzi gp85 glycoprotein superfamily with hundreds of members that have long been implicated in parasite cell invasion. Methodology/Principal Findings An in silico analysis was utilized to identify peptide motifs shared by the gp85 T. cruzi proteins and, using phage display, these selected peptide motifs were screened for their ability to bind to cells. One peptide, named TS9, showed significant cell binding capacity and was selected for further studies. Affinity chromatography, phage display and invasion assays revealed that peptide TS9 binds to cytokeratins and vimentin, and prevents T. cruzi cell infection. Interestingly, peptide TS9 and a previously identified binding site for intermediate filament proteins are disposed in an antiparallel beta-sheet fold, present in a conserved laminin-G-like domain shared by all members of the family. Moreover, peptide TS9 overlaps with an immunodominant T cell epitope. Conclusions/Significance Taken together, the present study reinforces previous results from our group implicating the gp85 superfamily of glycoproteins and the intermediate filament proteins cytokeratin and vimentin in the parasite infection process. It also suggests an important role in parasite biology for the conserved laminin-G-like domain, present in all members of this large family of cell surface proteins. (AU)

• FAPESP's process: 08/54806-8 - Identification of new molecular markers in angiogenic retina and rational design of new therapeutic agents for eye diseases with a vascular component
• Grantee: Ricardo Jose Giordano
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/16478-7 - Identification of Tryapanosoma cruzi novel genes important for host cell adhesion and invasion
• Grantee: Walter Colli
• Support Opportunities: Regular Research Grants