Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein.
Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein.
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分析甲霉素分泌蛋白的分析揭示了果糖1,6-三磷酸醛酸酶作为纤溶酶原结合蛋白。
DOI：
10.1186/s12866-015-0393-9
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发表时间：
2015-02-27
期刊：
影响因子：
4.2
通讯作者：
Soares CM
中科院分区：
文献类型：
--
作者：
Chaves EG;Weber SS;Báo SN;Pereira LA;Bailão AM;Borges CL;Soares CM
尽管是引起副球孢子菌病的重要热二形性真菌，但副球孢子菌属的致病机制仍然很大程度上未知。微生物病原体表达的分子可以与人纤溶酶原相互作用，人纤溶酶原是一种来自血浆的蛋白质，当被激活为纤溶酶时呈现纤溶活性。此外，纤溶酶具有降解细胞外基质成分的能力，有利于病原体扩散到更深的组织。我们小组之前的工作表明，副球孢子菌呈现烯醇酶，作为一种能够结合并激活纤溶酶原的蛋白质，增加病原体的纤溶活性，以及真菌粘附和入侵宿主细胞的潜力。通过使用蛋白质组分析，我们的目的是鉴定具有与纤溶酶原结合能力的副球孢子菌的其他蛋白质。在本研究中，我们采用分泌蛋白组的蛋白质组学分析来鉴定副球孢子菌 Pb01 的纤溶酶原结合蛋白。真菌分泌组中存在十五种蛋白质，具有与纤溶酶原结合的能力。这些蛋白质可能是真菌与宿主相互作用的目标。因此，它们可能会加剧真菌的侵袭。为了进行验证测试，我们选择了蛋白质果糖 1,6-二磷酸醛缩酶 (FBA)，在其他病原体中被描述为纤溶酶原结合蛋白。真菌表面的蛋白质 FBA 和重组 FBA (rFBA) 结合人纤溶酶原并促进其转化为纤溶酶，可能增加真菌的纤溶能力，如纤维蛋白降解测定所示。添加 rFBA 或抗 rFBA 抗体能够减少巨噬细胞和副球孢子菌之间的相互作用，这可能是通过阻断 FBA 的结合位点来实现的。这些数据揭示了 FBA 可能参与副球孢子菌的细胞粘附和组织侵袭/传播过程。这些数据表明副球孢子菌是一种具有多种纤溶酶原结合蛋白的病原体，这些蛋白可能在病原体-宿主相互作用中发挥重要作用。在这种情况下，FBA 是一种蛋白质，可能以某种方式参与感染期间真菌的入侵和传播过程。
Despite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to plasminogen. In the present study, we employed proteomic analysis of the secretome, in order to identify plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome, presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA. These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/dissemination of Paracoccidioides. These data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might be involved somehow in the processes of invasion and spread of the fungus during infection.
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影响因子：
--
作者：
Bhattacharya S;Ploplis VA;Castellino FJ
通讯作者：
Castellino FJ
影响因子：
3
作者：
Carneiro, LC;de Faria, FP;Soares, CMD
通讯作者：
Soares, CMD
影响因子：
4.8
作者：
Boone, Tyler J.;Tyrrell, Gregory J.
通讯作者：
Tyrrell, Gregory J.
影响因子：
2.6
作者：
Castro, Nadya Da Silva;Barbosa, Monica Santiago;de Almelda Soares, Celia Maria
通讯作者：
de Almelda Soares, Celia Maria
影响因子：
4.8
作者：
de la Paz Santangelo, Maria;Gest, Petra M.;Jackson, Mary
通讯作者：
Jackson, Mary