INVESTIGADORES
JAWERBAUM Alicia Sandra
artículos
Título:
Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection.
Autor/es:
DANIEL MUSIKANT; ROMINA HIGA; CRISTINA E RODRIGUEZ; MARTÍN EDREIRA; OSCAR CAMPETELLA; ALICIA JAWERBAUM; MARÍA S LEGUIZAMON
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 rele- vance 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 low (DTU I) and high virulence parasites induced a significant decrease in proMMP-9 plasma activity. Moreover, trans-sialidase, a rele- vant T. cruzi virulence factor, is involved in MMP-2 activity modulation both in vivo and in vitro. Itremoves a2,3-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.