Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection.
Musikant, D., Higa, R., Rodriguez, C. E., Edreira, M. M., Campetella, O., Jawerbaum, A. and Leguizamon, M. S.
Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160, C1428EGA, Ciudad de Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnologicas, Godoy Cruz 2290, C1425FQB, Ciudad de Buenos Aires, Argentina; Laboratorio de Reproduccion y Metabolismo, CEFYBO-CONICET, Facultad de Medicina Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Ciudad de Buenos Aires, Argentina.
Departamento de Microbiologia, IMPAM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Ciudad de Buenos Aires, Argentina.
Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160, C1428EGA, Ciudad de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnologicas, Godoy Cruz 2290, C1425FQB, Ciudad de Buenos Aires, Argentina; Instituto de Quimica Biologica de la Facultad de Ciencias Exactas y Naturales IQUIBICEN-CONICET, Universidad de Buenos Aires, Intendente Guiraldes 2160, C1428EGA, Ciudad de Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnologicas, Godoy Cruz 2290, C1425FQB, Ciudad de Buenos Aires, Argentina; Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, 25 de Mayo y Francia, B1650HMP, San Martin, Provincia de Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnologicas, Godoy Cruz 2290, C1425FQB, Ciudad de Buenos Aires, Argentina; Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, 25 de Mayo y Francia, B1650HMP, San Martin, Provincia de Buenos Aires, Argentina. Electronic address: sleguiza@unsam.edu.ar.
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 low (DTU I) and high 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 alpha2,3-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.
Biochimie 186: 82-93 (2021)