Abstract
BackgroundTSSA (Trypomastigote Small Surface Antigen) is an antigenic, adhesion molecule displayed on the surface of Trypanosoma cruzi trypomastigotes. TSSA displays substantial sequence identity to members of the TcMUC gene family, which code for the trypomastigote mucins (tGPI-mucins). In addition, TSSA bears sequence polymorphisms among parasite strains; and two TSSA variants expressed as recombinant molecules (termed TSSA-CL and TSSA-Sy) were shown to exhibit contrasting features in their host cell binding and signaling properties.Methods/Principle findingsHere we used a variety of approaches to get insights into TSSA structure/function. We show that at variance with tGPI-mucins, which rely on their extensive O-glycoslylation to achieve their protective function, TSSA seems to be displayed on the trypomastigote coat as a hypo-glycosylated molecule. This has a functional correlate, as further deletion mapping experiments and cell binding assays indicated that exposition of at least two peptidic motifs is critical for the engagement of the ‘adhesive’ TSSA variant (TSSA-CL) with host cell surface receptor(s) prior to trypomastigote internalization. These motifs are not conserved in the ‘non-adhesive’ TSSA-Sy variant. We next developed transgenic lines over-expressing either TSSA variant in different parasite backgrounds. In strict accordance to recombinant protein binding data, trypomastigotes over-expressing TSSA-CL displayed improved adhesion and infectivity towards non-macrophagic cell lines as compared to those over-expressing TSSA-Sy or parental lines. These phenotypes could be specifically counteracted by exogenous addition of peptides spanning the TSSA-CL adhesion motifs. In addition, and irrespective of the TSSA variant, over-expression of this molecule leads to an enhanced trypomastigote-to-amastigote conversion, indicating a possible role of TSSA also in parasite differentiation.Conclusion/SignificanceIn this study we provided novel evidence indicating that TSSA plays an important role not only on the infectivity and differentiation of T. cruzi trypomastigotes but also on the phenotypic variability displayed by parasite strains.
Highlights
Trypanosoma cruzi is the protozoan agent of Chagas disease, of major medical and economic significance throughout Latin America, and an emergent threat to global public health [1]
Infection with Trypanosoma cruzi produces a chronic and debilitating infectious disease known as Chagas disease, of major significance in Latin America and an emergent threat to global public health
One such candidate is the Trypomastigote Small Surface Antigen (TSSA), a polymorphic molecule expressed on the surface coat of infective trypomastigote forms
Summary
Trypanosoma cruzi is the protozoan agent of Chagas disease, of major medical and economic significance throughout Latin America, and an emergent threat to global public health [1]. This parasite alternates between blood-sucking triatomine vectors and a wide spectrum of susceptible, mammalian hosts, including humans. Epimastigote forms replicate along the digestive tract of insect vectors, and eventually attach to the cuticle of the rectal epithelium where they differentiate into non-dividing and infective metacyclic trypomastigotes These are in turn deposited on the mammal along with the insect feces during a blood meal and gain access to internal body fluids via a skin lesion or a mucosal surface. TSSA bears sequence polymorphisms among parasite strains; and two TSSA variants expressed as recombinant molecules (termed TSSA-CL and TSSA-Sy) were shown to exhibit contrasting features in their host cell binding and signaling properties
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call