Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection.
Sialic acid removal by trans-sialidase modulates MMP-2 activity during Trypanosoma cruzi infection.
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DOI：
10.1016/j.biochi.2021.04.005
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发表时间：
2021-07
期刊：
影响因子：
3.9
通讯作者：
Leguizamón MS
中科院分区：
文献类型：
--
作者：
Musikant D;Higa R;Rodríguez CE;Edreira MM;Campetella O;Jawerbaum A;Leguizamón MS
基质金属蛋白酶（MMPs）不仅在体内平衡过程中发挥相关作用，而且还参与了与感染性疾病相关的多种病理机制。由于它们在恰加斯病中的临床相关性最近被强调，我们研究了克氏锥虫感染对循环MMPs的调节。我们发现，从离散分型单位（DTU）VI的毒力寄生虫诱导更高的proMMP-2和MMP-2在血液中的活性，而低（DTU I）和高毒力寄生虫诱导proMMP-9血浆活性显着下降。此外，转唾液酸酶，一个相关的T。cruzi毒力因子参与体内和体外MMP-2活性调节。它从细胞表面糖缀合物中去除α 2，3-连接的唾液酸残基，然后触发PKC/MEK/ERK信号通路。此外，对这种唾液酸残基连接具有特异性的细菌唾液酸酶显示出相似的MMP调节谱，并触发相同的信号传导途径。这种新的致病机制，依赖于通过转唾液酸酶的神经氨酸酶活性去除唾液酸，可以被表达具有相似特异性的唾液酸酶的不同病原体利用。因此，在这里，我们提出了一个新的病原体的策略，通过调节MMP网络。
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.
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影响因子：
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