Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection

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...

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Bibliographic Details
Published in:Biochimie 2021-07, Vol.186, p.82-93
Main Authors: Musikant, Daniel, Higa, Romina, Rodríguez, Cristina E., Edreira, Martin M., Campetella, Oscar, Jawerbaum, Alicia, Leguizamón, María S.
Format: Article
Language:English
Subjects:
Chagas disease
Matrix metalloproteinases
Neuraminic acid
Neuraminidase
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Summary: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 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. •Virulent T. cruzi strains induce high levels of murine proMMP-2 and MMP-2 activity.•T. cruzi trans-sialidase/neuraminidase modulates MMP-2 activity in vivo.•T. cruzi sialidase removal of α2,3-linked sialic acid triggers PKC/MEK/ERK signaling.•Bacterial sialidases with the same specificity displayed MMP-2 modulation.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2021.04.005