scholarly journals Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes.

1992 ◽  
Vol 175 (2) ◽  
pp. 567-575 ◽  
Author(s):  
S Schenkman ◽  
L Pontes de Carvalho ◽  
V Nussenzweig
Keyword(s):  
Sialic Acid ◽  
Trypanosoma Cruzi ◽  
Transfer Reaction ◽  
Surface Membrane ◽  
Host Cells ◽  
Hydrolysis Of ◽  
Predominant Direction ◽  
Molecular Sieving ◽  
Free Sialic Acid ◽  
Single Enzyme

Trans-sialidase and neuraminidase activities have been detected on the surface membrane of trypomastigotes of Trypanosoma cruzi, and both have been implicated in the parasite's invasion of host cells. We show here that these enzymes are structurally related. They are recognized by two independently derived monoclonal antibodies, are anchored to the membrane by glycosylphosphatidylinositol, copurify by ion exchange, molecular sieving, and hydrophobic chromatography, have maximal activities between pH 6.5 and 7.5, and are inactivated by heating at 56 degrees C. Furthermore, the neuraminidase and trans-sialidase reactions are coupled. An increase of the concentration of acceptors of the transfer reaction decreases the amount of free sialic acid released through the neuraminidase reaction. We conclude that a single enzyme can catalyze the transfer or the hydrolysis of macromolecular-bound sialic acid. The predominant direction of the reaction will depend on the availability of appropriate oligosaccharide acceptors of sialic acid.

scholarly journals Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

2014 ◽  
Vol 10 ◽  
pp. 3073-3086 ◽  
Author(s):  
María Emilia Cano ◽  
Rosalía Agusti ◽  
Alejandro J Cagnoni ◽  
María Florencia Tesoriero ◽  
José Kovensky ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Trypanosoma Cruzi ◽  
High Performance ◽  
Transfer Reaction ◽  
Main Product ◽  
Amperometric Detection ◽  
Anion Exchange Chromatography ◽  
Competitive Inhibitor ◽  
Exchange Chromatography ◽  
Competitive Inhibitors

In this work we describe the synthesis of mono- and divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. The transfer reaction of sialic acid was performed using a recombinant TcTS and 3’-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3’-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. Most of the substrates behaved as good acceptors and moderate competitive inhibitors. A di-N-lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster.

scholarly journals Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment

2022 ◽  
Vol 11 ◽  
Author(s):  
Anny Carolline Silva Oliveira ◽  
Luisa Rezende ◽  
Vladimir Gorshkov ◽  
Marcella Nunes Melo-Braga ◽  
Thiago Verano-Braga ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Calcium Signaling ◽  
Surface Membrane ◽  
Host Cells ◽  
Biological Behavior ◽  
Membrane Repair ◽  
Phagocytic Cells ◽  
Membrane Injury ◽  
Injury Rates ◽  
Intracellular Environment

Trypanosoma cruzi invades non-professional phagocytic cells by subverting their membrane repair process, which is dependent on membrane injury and cell signaling, intracellular calcium increase, and lysosome recruitment. Cells lacking lysosome-associated membrane proteins 1 and 2 (LAMP1 and LAMP2) are less permissive to parasite invasion but more prone to parasite intracellular multiplication. Several passages through a different intracellular environment can significantly change T. cruzi’s gene expression profile. Here, we evaluated whether one single passage through LAMP-deficient (KO) or wild-type (WT) fibroblasts, thus different intracellular environments, could influence T. cruzi Y strain trypomastigotes’ ability to invade L6 myoblasts and WT fibroblasts host cells. Parasites released from LAMP2 KO cells (TcY-L2−/−) showed higher invasion, calcium signaling, and membrane injury rates, for the assays in L6 myoblasts, when compared to those released from WT (TcY-WT) or LAMP1/2 KO cells (TcY-L1/2−/−). On the other hand, TcY-L1/2−/− showed higher invasion, calcium signaling, and cell membrane injury rates, for the assays in WT fibroblasts, compared to TcY-WT and TcY-L1/2−/−. Albeit TcY-WT presented an intermediary invasion and calcium signaling rates, compared to the others, in WT fibroblasts, they induced lower levels of injury, which reinforces that signals mediated by surface membrane protein interactions also have a significant contribution to trigger host cell calcium signals. These results clearly show that parasites released from WT or LAMP KO cells are distinct from each other. Additionally, these parasites’ ability to invade the cell may be distinct depending on which cell type they interact with. Since these alterations most likely would reflect differences among parasite surface molecules, we also evaluated their proteome. We identified few protein complexes, membrane, and secreted proteins regulated in our dataset. Among those are some members of MASP, mucins, trans-sialidases, and gp63 proteins family, which are known to play an important role during parasite infection and could correlate to TcY-WT, TcY-L1/2−/−, and TcY-L2−/− biological behavior.

scholarly journals NanI Sialidase Can Support the Growth and Survival of Clostridium perfringens Strain F4969 in the Presence of Sialyated Host Macromolecules (Mucin) or Caco-2 Cells

2017 ◽  
Vol 86 (2) ◽  
Author(s):  
Jihong Li ◽  
Bruce A. McClane
Keyword(s):  
Sialic Acid ◽  
Clostridium Perfringens ◽  
Growth Promotion ◽  
Food Poisoning ◽  
Host Cells ◽  
Content Type ◽  
Growth And Survival ◽  
Gi Infections ◽  
Human Enterocyte ◽  
Free Sialic Acid

ABSTRACT Enterotoxin-producing Clostridium perfringens type A strains cause human gastrointestinal (GI) infections, including a very common food poisoning and 5 to 10% of all cases of antibiotic-associated diarrhea. This bacterium can utilize free sialic acid for growth, but most sialic acids in the GI tract are sequestered on macromolecules, such as the mucin proteins of mucus or glycoconjugates in host cells. However, many C. perfringens strains produce sialidases that might promote growth and survival by generating free sialic acid from those sialyated host macromolecules or by exposing underlying carbohydrates or proteins for digestion by other enzymes. The current study tested that possibility and found that the C. perfringens nonfoodborne human GI disease strain F4969 can use either a mucin preparation or Caco-2 cells, which are human enterocyte-like cells, to support its growth and survival. An isogenic nanI null mutant and complemented strain were used to show that this enhanced growth and survival using mucin or Caco-2 cells involved NanI, which is the major exosialidase of F4969 and many other C. perfringens strains. Experiments also suggested that, at least in part, this growth promotion involves utilization of NanI-generated sialic acid. In addition, a sialidase inhibitor named siastatin B reduced the growth and survival of F4969 growing with either the mucin preparation or Caco-2 cells. These findings suggest that, when produced, NanI may be a significant contributor to C. perfringens human GI infections by promoting the intestinal growth and survival of this bacterium. They also suggest the possibility that sialidase inhibitors might inhibit C. perfringens infections.

scholarly journals The Role of Sialic Acid-Binding Receptors (Siglecs) in the Immunomodulatory Effects ofTrypanosoma cruziSialoglycoproteins on the Protective Immunity of the Host

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Alexandre Morrot
Keyword(s):  
Sialic Acid ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cell Cycle Progression ◽  
Parasitic Infection ◽  
The United States ◽  
Host Cells ◽  
Health Concern ◽  
Lectin Receptors ◽  
Sialic Acid Binding

Chagas disease is caused by the protozoan parasiteTrypanosoma cruziand is an important endemic infection in Latin America. Lately, it has also become a health concern in the United States and Europe. Most of the immunomodulatory mechanisms associated with this parasitic infection have been attributed to mucin-like molecules on theT. cruzisurface. Mucins are high molecular weight glycoproteins that are involved in regulating diverse cellular activities in both normal and pathological conditions. InTrypanosoma cruziinfection, the parasite-derived mucins are the main acceptors of sialic acid and it has been suggested that they play a role in various host-parasite interactions during the course of Chagas disease. Recently, we have presented evidence that sialylation of the mucins is required for the inhibitory effects on CD4+T cells. In what follows we propose that signaling via sialic acid-binding Ig-like lectin receptors for these highly sialylated structures on host cells contributes to the arrest of cell cycle progression in the G1 phase and may allow the parasite to modulate the immune system of the host.

Basic Biology of Trypanosoma Cruzi

2020 ◽  
Vol 26 ◽  
Author(s):  
Aline Araujo Zuma ◽  
Emile dos Santos Barrias ◽  
Wanderley de Souza
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Structural Organization ◽  
Developmental Stages ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Cellular Organization ◽  
Basic Biology ◽  
Comparative Information

Abstract:: The present review addresses basic aspects of the biology of the pathogenic protozoa Trypanosoma cruzi and some comparative information with Trypanosoma brucei. Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts. However, these parasites present structural particularities. That is why the following topics are emphasized in this paper: developmental stages of the life cycle in the vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-pellicular microtubules; the flagellum and its attachment to the protozoan body through specialized junctions; the kinetoplast-mitochondrion complex, including its structural organization and DNA replication; the glycosome and its role in the metabolism of the cell; the acidocalcisome, describing its morphology, biochemistry, and functional role; the cytostome and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi complex; the nucleus, describing its structural organization during interphase and division; and the process of interaction of the parasite with host cells. The unique characteristics of these structures also make them interesting chemotherapeutic targets. Therefore, further understanding of cell biology aspects contributes to the development of drugs for chemotherapy.

Free Sialic Acid Storage Disease Mimicking Cerebral Palsy and Revealed by Blood Smear Examination

2011 ◽  
Vol 158 (1) ◽  
pp. 165-165.e1 ◽  
Author(s):  
François-Guillaume Debray ◽  
Caroline Lefebvre ◽  
Stéphanie Colinet ◽  
Karin Segers ◽  
René Stevens
Keyword(s):  
Cerebral Palsy ◽  
Sialic Acid ◽  
Blood Smear ◽  
Storage Disease ◽  
Smear Examination ◽  
Blood Smear Examination ◽  
Sialic Acid Storage Disease ◽  
Free Sialic Acid

scholarly journals Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

Biochimie ◽  
2021 ◽  
Vol 186 ◽  
pp. 82-93
Author(s):  
Daniel Musikant ◽  
Romina Higa ◽  
Cristina E. Rodríguez ◽  
Martin M. Edreira ◽  
Oscar Campetella ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Trypanosoma Cruzi ◽  
Cruzi Infection
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