IIBIO   27936
INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Unidad Ejecutora - UE
artículos
Título:
Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection
Autor/es:
MUSIKANT, DANIEL; EDREIRA, MARTIN M.; LEGUIZAMÓN, MARÍA S.; HIGA, ROMINA; CAMPETELLA, OSCAR; RODRÍGUEZ, CRISTINA E.; JAWERBAUM, ALICIA
Revista:
BIOCHIMIE
Editorial:
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Referencias:
Lugar: Paris; Año: 2021 vol. 186 p. 82 - 93
ISSN:
0300-9084
Resumen:
Matrix metalloproteinases (MMPs) not only play a relevant role in homeostatic processes but are also involved in several pathological mechanisms associated with infectious diseases. As their clinical relevance in Chagas disease has recently been highlighted, we studied the modulation of circulating MMPs by Trypanosoma cruzi infection. We found that virulent parasites from Discrete Typing Units (DTU) VI induced higher proMMP-2 and MMP-2 activity in blood, whereas both high and low (DTU I) virulence parasites induced a significant decrease in proMMP-9 plasma activity. Moreover, trans-sialidase, a relevant T. cruzi virulence factor, is involved in MMP-2 activity modulation both in vivo and in vitro. It removes α2,3-linked sialyl residues from cell surface glycoconjugates, which then triggers the PKC/MEK/ERK signaling pathway. Additionally, bacterial sialidases specific for this sialyl residue linkage displayed similar MMP modulation profiles and triggered the same signaling pathways. This novel pathogenic mechanism, dependent on sialic acid removal by the neuraminidase activity of trans-sialidase, can be exploited by different pathogens expressing sialidases with similar specificity. Thus, here we present a new pathogen strategy through the regulation of the MMP network.