title: Involvement of TSSA (trypomastigote small surface antigen) in Trypanosoma cruzi invasion of mammalian cells.
abstract: TSSA (trypomastigote small surface antigen) is a polymorphic mucin-like molecule displayed on the surface of Trypanosoma cruzi trypomastigote forms. To evaluate its functional properties, we undertook comparative biochemical and genetic approaches on isoforms present in parasite stocks from extant evolutionary lineages (CL Brener and Sylvio X-10). We show that CL Brener TSSA, but not the Sylvio X-10 counterpart, exhibits dose-dependent and saturable binding towards non-macrophagic cell lines. This binding triggers Ca(2+)-based signalling responses in the target cell while providing an anchor for the invading parasite. Accordingly, exogenous addition of either TSSA-derived peptides or specific antibodies significantly inhibits invasion of CL Brener, but not Sylvio X-10, trypomastigotes. Non-infective epimastigote forms, which do not express detectable levels of TSSA, were stably transfected with TSSA cDNA from either parasite stock. Although both transfectants produced a surface-associated mucin-like TSSA product, epimastigotes expressing CL Brener TSSA showed a ~2-fold increase in their attachment to mammalian cells. Overall, these findings indicate that CL Brener TSSA functions as a parasite adhesin, engaging surface receptor(s) and inducing signalling pathways on the host cell as a prerequisite for parasite internalization. More importantly, the contrasting functional features of TSSA isoforms provide one appealing mechanism underlying the differential infectivity of T. cruzi stocks.
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Universidad Nacional de San Martín-CONICET, San Martín, Buenos Aires, Argentina.
authors.forename: Gaspar E
authors.initials: GE
authors.lastname: Cánepa
authors.forename: Maria Sol
authors.initials: MS
authors.lastname: Degese
authors.forename: Alexandre
authors.initials: A
authors.lastname: Budu
authors.forename: Celia R S
authors.initials: CR
authors.lastname: Garcia
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buscaglia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D014349:Trypanosoma cruzi / Q000472:pathogenicity*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells
chemical_list: D014643:Variant Surface Glycoproteins, Trypanosoma; C573505:trypomastigote small surface antigen, Trypanosoma cruzi