Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome.
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 infection. All three mutants supported adhesion and infection to a much lower extent than the parental CHO cells. One of the mutants, Lec2, contains sugar chains terminating in non-reducing beta Gal residues, which are acceptors for sialylation by the T. cruzi trans-sialidase. Re-sialylation of Lec2 cells restored T. cruzi adhesion and invasion to about the same extent as wild-type cells. Digestion of wild-type cells with bacterial sialidase reduced T. cruzi interaction but after re-sialylation, the cells were almost as good as control, naturally sialylated parental cells. These results suggest that T. cruzi recognizes sialyl residues on the surface of host cells during invasion. On the other hand, affinity-purified trans-sialidase blocked T. cruzi adherence and invasion of sialylated cells, and had no effect on parasite interaction with sialic acid-deficient Lec2 mutant. Furthermore, 2,3-sialyllactose, a substrate for the trans-sialidase, competitively inhibited T. cruzi invasion of sialylated parental K1 cells, but 2,6-sialyllactose, which does not react with the trans-sialidase, was without effect, as were other sugars that do not contain alpha 2,3 sialyl residues. These results suggest that the trans-sialidase functions as a counter-receptor for trypomastigote binding to alpha 2,3-sialyl receptors on host cells as a prelude to T. cruzi invasion.
Ming
M
M
Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center Hospitals, Boston, MA.
Chuenkova
M
M
Ortega-Barria
E
E
Pereira
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002846:Chromatography, Affinity; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins; D007700:Kinetics; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009842:Oligopeptides; D012794:Sialic Acids / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D014709:Vero Cells
D006023:Glycoproteins; D009842:Oligopeptides; D012794:Sialic Acids; C069715:trans-sialidase; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid