The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells

Abstract

BackgroundChagas is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. On the order of seven million people are infected worldwide and current therapies are limited, highlighting the urgent need for new interventions. T. cruzi trypomastigotes can infect a variety of mammalian cells, recognition and adhesion to the host cell being critical for parasite entry. This study focuses on trypomastigote surface ligands involved in cell invasion.MethodsThree selection rounds of a phage peptide display library for isolation of phages that bind to trypomastigotes, resulted in the identification of the N3 dodecapeptide. N3 peptide binding to T. cruzi developmental forms (trypomastigotes, amastigotes and epimastigotes) was evaluated by flow cytometry and immunofluorescence assays. Parasite invasion of Vero cells was assessed by flow cytometry and immunofluorescence assays.ResultsPhage display screening identified the N3 peptide that binds preferentially to the surface of the trypomastigote and amastigote infective forms as opposed to non-infective epimastigotes. Importantly, the N3 peptide, but not a control scrambled peptide, inhibits trypomastigote invasion of Vero cells by 50%.ConclusionThe N3 peptide specifically binds to T. cruzi, and by doing so, inhibits Vero cell infection. Follow-up studies will identify the molecule on the parasite surface to which the N3 peptide binds. This putative T. cruzi ligand may advance chemotherapy design and vaccine development.

Peptide selection via phage display to inhibit Leishmania-macrophage interactions

“…Therefore, characterization of the initial ligand-receptor interaction of each parasite species is likely to lead to mechanistic insights into downstream disease pathways (Carneiro and Peters, 2021;Mann et al, 2021). Molecular identification of ligand-receptor interaction for parasite-host cell recognition can be initiated by selecting peptides that interfere with this specific interaction (Ghosh et al, 2009(Ghosh et al, , 2011Cha et al, 2015Cha et al, , 2016Cha et al, , 2021de Paula et al, 2022). Here, we used a phage peptide display approach to select peptides that bind to the surface of L. amazonensis, L. infantum, or both MP species, the parasite form responsible for initiating mammalian host infection.…”