Role of the gp85/trans-sialidases in Trypanosoma cruzi tissue tropism: preferential binding of a conserved peptide motif to the vasculature in vivo.
BACKGROUND
Transmitted by blood-sucking insects, the unicellular parasite Trypanosoma cruzi is the causative agent of Chagas' disease, a malady manifested in a variety of symptoms from heart disease to digestive and urinary tract dysfunctions. The reasons for such organ preference have been a matter of great interest in the field, particularly because the parasite can invade nearly every cell line and it can be found in most tissues following an infection. Among the molecular factors that contribute to virulence is a large multigene family of proteins known as gp85/trans-sialidase, which participates in cell attachment and invasion. But whether these proteins also contribute to tissue homing had not yet been investigated. Here, a combination of endothelial cell immortalization and phage display techniques has been used to investigate the role of gp85/trans-sialidase in binding to the vasculature.


METHODS
Bacteriophage expressing an important peptide motif (denominated FLY) common to all gp85/trans-sialidase proteins was used as a surrogate to investigate the interaction of this motif with the endothelium compartment. For that purpose phage particles were incubated with endothelial cells obtained from different organs or injected into mice intravenously and the number of phage particles bound to cells or tissues was determined. Binding of phages to intermediate filament proteins has also been studied.


CONCLUSIONS
Our data indicate that FLY interacts with the endothelium in an organ-dependent manner with significantly higher avidity for the heart vasculature. Phage display results also show that FLY interaction with intermediate filament proteins is not limited to cytokeratin 18 (CK18), which may explain the wide variety of cells infected by the parasite. This is the first time that members of the intermediate filaments in general, constituted by a large group of ubiquitously expressed proteins, have been implicated in T. cruzi cell invasion and tissue homing.
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Renata R
RR
Tonelli
Ricardo J
RJ
Giordano
Elena Magda
EM
Barbu
Ana Claudia
AC
Torrecilhas
Gerson S
GS
Kobayashi
Robert R
RR
Langley
Wadih
W
Arap
Renata
R
Pasqualini
Walter
W
Colli
Maria Júlia M
MJ
Alves
D020816:Amino Acid Motifs; D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000378:metabolism / Q000469:parasitology*; D042783:Endothelial Cells / Q000378:metabolism / Q000469:parasitology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018523:Tropism; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000502:physiology
D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D015800:Protozoan Proteins; C069715:trans-sialidase; D009439:Neuraminidase