Inactive trans-Sialidase Expression in iTS-null Trypanosoma cruzi Generates Virulent Trypomastigotes.
Inactive trans-Sialidase Expression in iTS-null Trypanosoma cruzi Generates Virulent Trypomastigotes.
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DOI：
10.3389/fcimb.2017.00430
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发表时间：
2017
影响因子：
5.7
通讯作者：
Leguizamón MS
中科院分区：
文献类型：
--
作者：
Pascuale CA;Burgos JM;Postan M;Lantos AB;Bertelli A;Campetella O;Leguizamón MS
为了更好地了解病原体与宿主相互作用的致病机制，需要公开病原体的毒力因子。就克氏锥虫而言，有几个分子与毒力有关。其中，转唾液酸酶（TS）因其对免疫系统的影响以及参与宿主细胞的相互作用/入侵而成为特别相关的酶之一。令人费解的是，编码无活性 TS (iTS) 同种型的保守基因的存在仅限于来自离散分型单位 TcII、TcV 和 TcVI 的寄生虫基因组，其中包括高毒力菌株。先前使用重组 iTS 的体外结果支持该异构体可以发挥与酶活性蛋白不同或互补的致病作用。然而，仍缺乏涉及 iTS 体内发病机制和侵袭的直接证据。在这里，我们通过用重组基因转染 iTS-null 寄生虫来应对这一挑战，该重组基因使我们能够跟踪其表达及其与病理事件的关联。我们发现 iTS 表达可改善寄生虫对宿主细胞的侵袭，并增加其对小鼠的体内毒力，如心脏和骨骼肌的组织病理学结果所示。
Disclosing virulence factors from pathogens is required to better understand the pathogenic mechanisms involved in their interaction with the host. In the case of Trypanosoma cruzi several molecules are associated with virulence. Among them, the trans-sialidase (TS) has arisen as one of particular relevance due to its effect on the immune system and involvement in the interaction/invasion of the host cells. The presence of conserved genes encoding for an inactive TS (iTS) isoform is puzzlingly restricted to the genome of parasites from the Discrete Typing Units TcII, TcV, and TcVI, which include highly virulent strains. Previous in vitro results using recombinant iTS support that this isoform could play a different or complementary pathogenic role to that of the enzymatically active protein. However, direct evidence involving iTS in in vivo pathogenesis and invasion is still lacking. Here we faced this challenge by transfecting iTS-null parasites with a recombinant gene that allowed us to follow its expression and association with pathological events. We found that iTS expression improves parasite invasion of host cells and increases their in vivo virulence for mice as shown by histopathologic findings in heart and skeletal muscle.
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影响因子：
4.3
作者：
Cremona, ML;Campetella, O;Frasch, ACC
通讯作者：
Frasch, ACC
影响因子：
2.1
作者：
De Lima, Ana R.;Navarroa, Maria C.;Contreras, Victor T.
通讯作者：
Contreras, Victor T.
影响因子：
6.7
作者：
Lantos, Andres B.;Carlevaro, Giannina;Campetella, Oscar
通讯作者：
Campetella, Oscar
影响因子：
4.8
作者：
Di Noia, JM;D'Orso, I;Frasch, ACC
通讯作者：
Frasch, ACC
影响因子：
6.4
作者：
Leguizamón, MS;Mocetti, E;Campetella, O
通讯作者：
Campetella, O