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Trypanosoma cruzi infection inhibited by peptides modeled from a fibronectin cell attachment domain
Abstract:
The mechanism by which Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, becomes attached to mammalian cells is not well understood. Fibronectin is thought to participate in the attachment, and in this study the region of fibronectin that interacts with the surface receptors of T. cruzi trypomastigotes was investigated by testing the binding of the amino acid sequence Arg-Gly-Asp-Ser, corresponding to the cell attachment site of fibronectin to T. cruzi trypomastigotes. Peptides with the sequence Arg-Gly-Asp-Ser, but not Arg-Phe-Asp-Ser, Arg-Phe-Asp-Ser-Ala-Ala-Arg-Phe-Asp, Ser-Lys-Pro, Glu-Ser-Gly, or Ala-Lys-Thr-Lys-Pro, bound to the parasite surface and inhibited cell invasion by the pathogen. Monoclonal antibodies to the cell attachment domain of fibronectin also inhibited cell infection by the parasite. The immunization of BALB/c mice with tetanus toxoid-conjugated peptide induced a significant protection against T. cruzi. The data support the notion that the sequence Arg-Gly-Asp-Ser of cell surface fibronectin acts as a recognition site for attachment of the parasites.
Insights
The Arg-Gly-Asp-Ser sequence on fibronectin helps Trypanosoma cruzi attach to cells. This finding offers insights into Chagas
Area of Science:
- Parasitology
- Molecular Biology
- Immunology
Background:
- Chagas' disease is caused by Trypanosoma cruzi.
- The attachment mechanism of T. cruzi to host cells is not fully understood.
- Fibronectin is implicated in parasite attachment.
Purpose of the Study:
- To investigate the specific region of fibronectin involved in T. cruzi attachment.
- To identify the molecular interactions between T. cruzi and fibronectin.
Main Methods:
- Testing the binding of fibronectin-derived peptides to T. cruzi.
- Using monoclonal antibodies against fibronectin's cell attachment domain.
- Immunizing mice with a peptide-conjugated vaccine.
Main Results:
- The Arg-Gly-Asp-Ser peptide specifically bound to T. cruzi and inhibited cell invasion.
- Other tested peptides did not bind or inhibit invasion.
- Monoclonal antibodies also blocked parasite infection.
- Vaccination with the peptide conferred protection against T. cruzi.
Conclusions:
- The Arg-Gly-Asp-Ser sequence in fibronectin serves as a recognition site for T. cruzi attachment.
- This interaction is crucial for parasite invasion of mammalian cells.
- Targeting this sequence holds potential for Chagas' disease therapeutics.