A novel T. cruzi heparin-binding protein promotes fibroblast adhesion and penetration of engineered bacteria and trypanosomes into mammalian cells

Ortega-Barrı́a, Eduardo; Pereira, M. E. A.

doi:10.1016/0092-8674(91)90192-2

Cited by 200 publications

(140 citation statements)

References 29 publications

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“…41), including viruses, protozoan parasites, and bacterial pathogens (19,25,(42)(43)(44). These interactions fall into two classes: (a) Trypanosoma cruzi (19), Leishmania donovani (43), Borrelia burgdorferi (20,44), and some herpesvirus (42) bind directly to mammalian cell surface proteoglycans; and (b) Chlamydia trachomatis (25) employs a different mechanism in which attachment to, and subsequent infectivity of, eukaryotic cells is dependent on a heparan sulfate-like ligand on the surface of the organism that bridges acceptors on the microorganism and host cell surface membranes, facilitating cell-cell contact. It has been proposed that the heparan sulfatelike adhesin is synthesized by Chlamydia (25).…”

Section: Discussionmentioning

confidence: 99%

“…gondii Attachment Assay-T. gondii attachment was determined using confluent monolayers of animal cell mutants pgsA-745 and pgsB-761, which are defective in glycosaminoglycan biosynthesis, and wild type K1 cells grown in 24-well tissue culture plates (Falcon) fixed by addition of 1% glutaraldehyde (19). Toxoplasma tachyzoites were harvested, preincubated in methionine-free DMEM for 30 min at 37°C, and metabolically labeled by addition of 250 Ci/ml of [ 35 S]methionine for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

Ortega-Barrı́a

Boothroyd²

1999

Journal of Biological Chemistry

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106

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Toxoplasma gondii is one of the most widespread parasites of humans and animals. The parasite has a remarkable ability to invade a broad range of cells within its mammalian hosts by mechanisms that are poorly understood at the molecular level. This broad host cell specificity suggests that adhesion should involve the recognition of ubiquitous surface-exposed host molecules or, alternatively, the presence of various parasite attachment molecules able to recognize different host cell receptors. We have discovered a sugar-binding activity (lectin) in tachyzoites of T. gondii that plays a role in vitro in erythrocyte agglutination and infection of human fibroblasts and epithelial cells. The ability to agglutinate erythrocytes can be reversed by a variety of soluble glycoconjugates, of which heparin, fucoidan, and dextran sulfate were the most effective. Interestingly, infectivity of tachyzoites for human foreskin fibroblasts, cells that are commonly used to grow T. gondii in vitro, was increased by low concentrations of the sulfated glycoconjugates that inhibited hemagglutination activity (i.e. dextran sulfate and fucoidan) whereas high concentrations inhibited parasite infection. Furthermore, inhibition of glycosaminoglycan biosynthesis and sulfation on the host cells reduced Toxoplasma infectivity. Finally, Toxoplasma tachyzoites showed a reduced ability to infect epithelial cell mutants deficient in the biosynthesis of surface proteoglycans. The probable identity of the hemagglutinin(s) was investigated by 1) direct binding of red blood cells to filter blots of Toxoplasma proteins separated by polyacrylamide gel electrophoresis, and 2) binding of metabolically labeled parasite proteins to fixed mammalian cells. Three parasite bands were thus identified as candidate adhesins. These results suggest that attachment of T. gondii to its target cell is mediated by parasite lectins and that sulfated sugars on the surface of host cells may function as a key parasite receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

Ortega-Barrı́a

Boothroyd²

1999

Journal of Biological Chemistry

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106

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“…Heparan sulfate-containing proteoglycans on eukaryotic cells have been shown to facilitate microbial adherence and/or cellular invasion for human immunodeficiency virus (1), herpes simplex virus (2,3), cytomegalovirus (4,5), varicella zoster virus (6), Bordetella pertussis (7), Leishmania donovani (8,9), Trypanosoma cruzi (10), and Plasmodium circumsporozoites (11). Unlike each of these other microbial pathogens, it has recently been shown that Chlamydia trachomatis attachment to, and subsequent infectivity of, eukaryotic cells is dependent upon the presence of a heparan sulfate-like ligand on the surface of the organism (12,13).…”

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confidence: 99%

Structural Requirements of Heparin Binding to Chlamydia trachomatis

Chen

Zhang

Stephens

1996

Journal of Biological Chemistry

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“…Another surface molecule of T. cruzi trypomastigotes with affinity for extracellular matrix components is penetrin, a 60 kDa protein that selectively binds to heparin, heparin sulfate and collagen, and promotes fibroblast adhesion and penetration (59). Recombinant penetrin, expressed in Escherichia coli and localized on its surface, induced bacterial attachment to and penetration into Vero cells in a proteoglycan-and collagen-inhibitable manner (59).…”

Section: Penetrinmentioning

confidence: 99%

“…The candidate trypomastigote ligands for structural and atomic analysis are TS, TS-like molecules (36,53,57), mucins (58), heparin binding protein (59), and surface casein kinase II substrates (60) that bind to nonphagocytic cells, kinases and to extracellular matrix proteins (52)(53)(54)(55)(56)(57)(58)(59)(60)(61) and to host cell receptors on non-phagocytic cells in order to invade them (52)(53)(54)(55)(56)(57). It is thought that trypanosome trans-sialidases transfer sialic acids to trypanosome mucins and serve as acceptors of sialic acids during infection.…”

Section: Trans-sialidases and Trans-sialidase Like Moleculesmentioning

confidence: 99%

Molecular analysis of early host cell infection by Trypanosoma cruzi

Villalta¹

2008

Front Biosci

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Trypanosoma cruzi, the causative agent of Chagas heart disease, infects heart and other cells leading to cardiac arrest frequently followed by death (1). The disease affects millions of individuals in the Americas and is posing health problems because of blood transmission in the US due to large Latin American immigration (2-3). Since the current drugs present serious side effects and do not cure the chronic infection (4), it is critically important to understand the early process of cellular infection at the molecular and structural levels to design novel inhibitors to block T. cruzi infection. In this review, the authors critically analyze the molecular and cellular basis of early T. cruzi infection and discuss the future directions in this area. The candidate T. cruzi invasive genes and host genes involved in the process of early infection are just beginning to be understood. The trypanosome invasive proteins are excellent targets for intervention. The progress made in the cell biology of T. cruzi infection will also facilitate the development of novel cell-based therapies to ameliorate the disease.

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A novel T. cruzi heparin-binding protein promotes fibroblast adhesion and penetration of engineered bacteria and trypanosomes into mammalian cells

Cited by 200 publications

References 29 publications

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

Structural Requirements of Heparin Binding to Chlamydia trachomatis

Molecular analysis of early host cell infection by Trypanosoma cruzi

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