A novel T. cruzi heparin-binding protein promotes fibroblast adhesion and penetration of engineered bacteria and trypanosomes into mammalian cells.
T. cruzi invades mammalian cells in various organs after migrating through the ECM. These activities appear to be mediated by a unique 60 kd protein exposed on the T. cruzi surface, which promotes selective adhesion of trypomastigotes to three ECM components: heparin, heparan sulfate, and collagen. The affinity-purified protein binds to host fibroblasts in a saturable and glycosaminoglycan- and collagen-inhibitable manner. When adsorbed to plastic, it promotes adhesion and spreading of fibroblasts, as does the recombinant protein expressed in E. coli. The endogenous protein, and reactive ECM proteins, are very effective in preventing T. cruzi invasion of culture cells. The recombinant protein localizes on the E. coli surface and induces the bacteria that express it to adhere to and penetrate nonphagocytic Vero cells in a proteoglycan- and collagen-inhibitable manner. Therefore, the protein, named penetrin, could play a critical role in T. cruzi binding to the ECM and to cells, and in host cell invasion.
Ortega-Barria
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Department of Medicine, Tufts-New England Medical Center Hospitals, Boston, Massachusetts 02111.
Pereira
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D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002847:Chromatography, Agarose; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism / Q000469:parasitology; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology*; D006025:Glycosaminoglycans / Q000378:metabolism / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism / Q000494:pharmacology; D008854:Microscopy, Electron; D011509:Proteoglycans / Q000378:metabolism; D015800:Protozoan Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells
D003094:Collagen; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D011509:Proteoglycans; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C037680:heparin receptor