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

Abstract

BackgroundChagas' 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 FindingsAn 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 β-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/SignificanceTaken 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.

Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection

“…Nonetheless, some general observations offer insight into lifestyle differences among these different parasite stages. For example, trypomastigotes uniquely express a number of protein kinases and an intermediate filament-binding trichohyalin-like protein [ 43 ], which may reflect specialized capacities linked to host cell recognition, signaling and invasion by this parasite life stage [ 44 – 46 ]. Epimastigotes express twice as many genes in a stage-selective manner as the other parasite life stages ( S8 Table ), many of which encode metabolic enzymes (eg.…”

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

“…Since main differences in EVs derived from YuYu and Y strains were in proteins known to act during the processes of cell adhesion and infection [5,22,27,28], their role during invasion was evaluated in phagocytic J774A.1 macrophages and non‐phagocytic LLC‐MK2 cells. Cells were pre‐incubated for 1 h with EVs from both strains and then exposed to TCT of the Y strain for 2 h. EVs from Y strain increased the number of J774A.1 macrophages infected with T. cruzi (Figure 7(a)).…”

Identification of relevant prognostic values of cytokeratin 20 and cytokeratin 7 expressions in lung cancer

“…Cell cytokeratin (CK) is a main cytoskeletal protein in the keratinocyte that is mainly distributed in the epithelial cells, maintaining the integrity and continuity of the epithelial tissue is the major function of such type of structural protein [ 11 , 12 ]. Studies have found that CK is highly conserved and differentiated, closely related to the proliferation and differentiation of epithelial cells [ 13 ]. At present, there are more than 20 kinds of confirmed subtypes distributed in epithelial cells of different organs [ 14 ].…”