Studies of Trypanosoma cruzi trans-sialidase using transfection method

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Trypanosoma cruzi trans-sialidase catalyzes the transfer of a(2-3) linked sialic acid from host derived glycoconjugates to the parasite surface mucin-like acceptor molecules and vice versa. Several lines of evidence suggest that trans-sialidase and sialylated molecules on the parasite and host cell surface are important for cell invasion and parasite escape from host defense systems. The enzyme expressed in infective trtpomastigote stage (T-TS) is located on the parasite surface through a glycosyl phosphatididylinositol (GPI) anchor, and readily shed into culture supernatant in vitro and into the bloodstream of animals in, vivo. On the other hands, trans-sialidase is also detectable in noninfective epimastigote stage, however this is not released into the medium nor recognized by antibodies against the carboxyl terminal repeats of T-TS. Actually, there are two types of trans-sialidase gene families, which are localized at different chromosomes and controlled under different regulation. … More We have studied functions, molecular mechanisms of expression and localization of these two different types of trans-sialidases.We have obtained several genes of these two families and prepared some derivatives, hybrid trans-sialidase molecules based on comparison. Both N-terminal sequences of these two types, in which there are no similarities, are highly hydrophobic and functioned as signal peptides of secretary and membrane proteins. C-terminal hydrophobic region of T-TS which is replaced by GPI-anchor structure seems to be not important for secretion. The structural feature of N- and C-terminal regions of trans-sialidase expressed in epimastigote (E-TS) are similar to those of T-TS. Molecular studies of different localization of two TS even structural similarity are ongoing using hybrid molecules and molecular tag epitope.The collaboration research with Dr. Pereira, Tafts University could have shown that T-TS C-terminal repeats induce IL-6 secretion from human endothelial cells and peripheral blood mononuclear cells. Less