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Trypanosoma cruzi, the etiological agent of Chagas' disease, expresses a trans-sialidase at highest levels in infective trypomastigotes, where it attaches to the plasma membrane by a glycophosphoinositol linkage. Bound enzyme sheds into the extracellular milieu in a soluble form. Experiments performed in vitro suggest that the trans-sialidase participates(More)
The substrate specificity, physico-chemical, and kinetic properties of the trans-sialidase from Trypanosoma cruzi have been investigated. The enzyme demonstrates activity towards a wide range of saccharide, glycolipid, and glycoprotein acceptors which terminate with a beta-linked galactose residue, and synthesizes exclusively an alpha 2-3 sialosidic(More)
Patients infected with Trypanosoma cruzi may remain asymptomatic for decades and show signs of neuroregeneration in the peripheral nervous system (PNS). In the absence of such neuroregeneration, patients may die in part by extensive neuronal destruction in the gastrointestinal tract. Thus, T. cruzi may, despite their invasion of the PNS, directly prevent(More)
TrkA is a receptor tyrosine kinase activated primarily by nerve growth factor (NGF) to regulate differentiation, survival, and other important functions of neurons. Given the critical role TrkA plays in neural maintenance, it may be that microbial invaders of the nervous system utilize this receptor to reduce tissue damage for maximizing host-parasite(More)
Despite the neuronal degeneration in the chronic stage of Chagas' disease, neuron counts actually increase in the preceding, asymptomatic stage, in contrast to the age-related decrease in neuron counts in age-matched normal individuals. Relevant to this observation, we found that the trans-sialidase (TS) of Trypanosoma cruzi, the etiologic agent of Chagas'(More)
Trypanosoma cruzi attaches and invades a large variety of mammalian cells. The nature of the cell receptors and of the corresponding parasite counter-receptors that mediate T. cruzi-host cell interaction are not known. Three sialic acid-deficient mutants of Chinese hamster ovary (CHO) cells were used to probe the role of host sialyl residues in T. cruzi(More)
A parasite-derived neurotrophic factor (PDNF) produced by the Chagas' disease parasite Trypanosoma cruzi binds nerve growth factor (NGF) receptor TrkA, increasing receptor autophosphorylation, and activating phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK/Erk) pathways, and transcription factor CREB. The end-result is(More)
The parasite Trypanosoma cruzi, which causes Chagas' disease, differentiates in the cytosol of its host cell and then replicates and spreads infection, processes that require the long-term survival of the infected cells. Here, we show that in the cytosol, parasite-derived neurotrophic factor (PDNF), a trans-sialidase that is located on the surface of T.(More)
The trans-sialidase (TS) of Trypanosoma cruzi induces survival and differentiation of neuronal and glial cells. This mechanism underlying survival is via phosphatidylinositol 3-kinase (PI3K) but how TS promotes neuronal differentiation remained to be determined. Here we show that TS-induced neurite outgrowth in PC12 cells is through sustained activation of(More)
The neuraminidase/trans-sialidase of Trypanosoma cruzi, the agent of Chagas' disease, promotes differentiation and survival of growth factor-deprived neuronal and glial cells. To gain further insights into the possible neuroprotection of this parasite-derived counterpart of neurotrophic factors (PDNF), we sought to determine whether it mimics growth factors(More)