The Trypomastigote Small Surface Antigen (TSSA) regulates Trypanosoma cruzi infectivity and differentiation.
The Trypomastigote Small Surface Antigen (TSSA) regulates Trypanosoma cruzi infectivity and differentiation.
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锥虫小型表面抗原（TSSA）调节了克鲁兹锥虫的感染性和分化。
DOI：
10.1371/journal.pntd.0005856
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发表时间：
2017-08
影响因子：
3.8
通讯作者：
Buscaglia CA
中科院分区：
文献类型：
--
作者：
Cámara MLM;Cánepa GE;Lantos AB;Balouz V;Yu H;Chen X;Campetella O;Mucci J;Buscaglia CA
TSSA (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. Here 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. In 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. 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. In the absence of vaccines and/or appropriate chemotherapies, the search for parasite effectors that support infection of mammalian cells is a focus of significant interest. One such candidate is the Trypomastigote Small Surface Antigen (TSSA), a polymorphic molecule expressed on the surface coat of infective trypomastigote forms. Previous data indicated that recombinant versions of two different TSSA variants (termed TSSA-CL and TSSA-Sy) encoded by parasite strains belonging to extant phylogenetic groups exhibited contrasting host cell binding and signaling abilities. Here, we generated genetically modified strains of T. cruzi over-expressing different TSSAs to address this issue. Trypomastigotes over-expressing TSSA-CL, the ‘adhesive variant’, displayed improved adhesion and infectivity towards non-macrophagic cell lines as compared to those over-expressing TSSA-Sy or parental lines. In addition, and irrespective of the protein variant, TSSA over-expression enhanced trypomastigote-to-amastigote conversion. Overall, our data strongly suggest 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 different strains of this parasite. These data, together with the fact that TSSA recalls a strong and likely protective humoral response during human infections, support this molecule as an excellent candidate for molecular intervention and/or vaccine development in Chagas disease.
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影响因子：
2.4
作者：
Bustos, Patricia L.;Perrone, Alina E.;Bua, Jacqueline
通讯作者：
Bua, Jacqueline
影响因子：
1.5
作者：
Campo, V;Di Noia, JM;Frasch, ACC
通讯作者：
Frasch, ACC
影响因子：
14.9
作者：
Bartholomeu, Daniella C.;Cerqueira, Gustavo C.;El-Sayed, Najib M.
通讯作者：
El-Sayed, Najib M.
影响因子：
4.1
作者：
ALMEIDA, IC;FERGUSON, MAJ;TRAVASSOS, LR
通讯作者：
TRAVASSOS, LR
影响因子：
3.7
作者：
Cruz MC;Souza-Melo N;da Silva CV;Darocha WD;Bahia D;Araújo PR;Teixeira SR;Mortara RA
通讯作者：
Mortara RA