PPE38 of Mycobacterium marinum triggers the cross-talk of multiple pathways involved in the host response, as revealed by subcellular quantitative proteomics.
PPE38 of Mycobacterium marinum triggers the cross-talk of multiple pathways involved in the host response, as revealed by subcellular quantitative proteomics.
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亚细胞定量蛋白质组学揭示，海分枝杆菌的 PPE38 会触发参与宿主反应的多种途径的串扰。
DOI：
10.1021/pr301017e
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发表时间：
2013-05-03
影响因子：
4.4
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Wang H;Dong D;Tang S;Chen X;Gao Q
PE/PPE家族蛋白质在致病性物种如结核分枝杆菌和分枝杆菌中高丰度。marinum在产生抗原变异和逃避宿主免疫应答中起关键作用。然而，很少有人知道他们的功能作用，在分枝杆菌的发病机制。以前，我们发现PPE 38与分枝杆菌的毒力相关，推测是通过调节宿主免疫反应。为了阐明PPE 38与宿主反应之间的联系，我们采用了亚细胞，氨基酸编码的质量标签（AACT）/SILAC为基础的定量蛋白质组学方法，以确定蛋白质组的变化，在主机响应M。marinum PPE 38.结果，分别发现291或290个蛋白质在细胞核中上调或下调。同时，在细胞质中分别检测到576个上调和272个下调蛋白。定量蛋白质组学变化和同步生物学验证的数据表明，M。结论：海洋植物PPE 38可能通过与Toll样受体2（TLR 2）相互作用而引起巨噬细胞广泛的炎症反应。我们还发现，PPE 38可以阻止感染的巨噬细胞中MHC-1的加工和呈递。利用生物信息学工具分析宿主蛋白质组的全局变化，我们获得了一个涉及各种转录因子（TF）和TF相关蛋白的PPE 38-respondor网络。我们的系统研究结果表明，存在涉及广泛的不同生物学途径/过程的串扰，这些生物学途径/过程协调宿主对M的反应。marinum PPE 38.
The PE/PPE family of proteins which are in high abundance in pathogenic species such as Mycobacterium tuberculosis and M. marinum, play the critical role in generating antigenic variation and evasion of host immune responses. However, little is known about their functional roles in mycobacterial pathogenesis. Previously, we found that PPE38 is associated with the virulence of mycobacteria, presumably by modulating the host immune response. To clarify the link between PPE38 and host response, we employed a subcellular, amino acid-coded mass tagging (AACT)/SILAC-based quantitative proteomic approach to determine the proteome changes during host response to M. marinum PPE38. As a result, 291 or 290 proteins were found respectively to be up- or down-regulated in the nucleus. Meanwhile, 576 upregulated and 272 downregulated proteins were respectively detected in the cytosol. The data of quantitative proteomic changes and concurrent biological validations revealed that M. marinum PPE38 could trigger extensive inflammatory responses in macrophages, probably through interacting with toll-like receptor 2 (TLR2). We also found that PPE38 may arrest MHC-1 processing and presentation in infected macrophages. Using bioinformatics tools to analyze global changes in the host proteome, we obtained a PPE38-respondor network involved in various transcriptional factors (TFs) and TF-associated proteins. The results of our systems investigation now indicate that there is cross-talk involving a broad range of diverse biological pathways/processes that coordinate the host response to M. marinum PPE38.
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影响因子：
14.9
作者：
Esensten, JH;Tsytsykova, AV;Lopez-Rodriguez, C;Ligeiro, FA;Rao, A;Goldfeld, AE
通讯作者：
Goldfeld, AE
影响因子：
3.7
作者：
Abarca-Rojano, E;Rosas-Medina, P;Sánchez-García, FJ
通讯作者：
Sánchez-García, FJ
影响因子：
7.4
作者：
Chen, X;Smith, LM;Bradbury, EM
通讯作者：
Bradbury, EM
影响因子：
7.4
作者：
Ibarrola, N;Kalume, DE;Pandey, A
通讯作者：
Pandey, A
影响因子：
5.8
作者：
Balaji, Kithiganahalli N.;Goyal, Girija;Mohammad, Saleemulla
通讯作者：
Mohammad, Saleemulla