The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to subvert cell death and activate cell survival pathways.
The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to subvert cell death and activate cell survival pathways.
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DOI：
10.1126/scisignal.aal4501
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发表时间：
2017-05-16
影响因子：
7.3
通讯作者：
Orth K
中科院分区：
文献类型：
--
作者：
De Nisco NJ;Kanchwala M;Li P;Fernandez J;Xing C;Orth K
细菌效应物是宿主信号通路的有效操纵者。海洋细菌副溶血性弧菌（V. para）通过两种三型分泌系统（T3SS）将效应器输送到宿主细胞中。无处不在的T3SS1对V. para在环境中的生存至关重要，而T3SS2在人类宿主中引起急性胃肠炎。虽然自然宿主不明确，但T3SS1效应物攻击高度保守的细胞过程和途径，以协调非凋亡细胞死亡。关于T3SS1效应物如何单独发挥作用，我们知道的很多，但我们想了解它们是如何协同作用全局影响宿主细胞信号传导的。为了评估宿主对T3SS1的反应，我们比较了感染有T3SS1功能的V. para成纤维细胞（T3SS1+）与感染缺乏T3SS1的V. para成纤维细胞（T3SS1−）的基因表达随时间的变化。总体而言，宿主对T3SS1+和T3SS1−V. para的转录反应都是快速、稳健和时间动态的。T3SS1通过特异性改变398个基因的表达来重新连接宿主基因表达。虽然T3SS1效应物在翻译后水平靶向宿主细胞，引起细胞毒性，但网络分析表明，V. para T3SS1也会引发宿主转录反应，最初激活细胞存活并抑制细胞死亡网络。T3SS1介导的几种关键促存活转录物的表达增加依赖于宿主信号通路，该通路在感染后期被T3SS1的翻译后作用沉默。综上所述，我们的分析揭示了T3SS1作为宿主细胞信号传导的转录和翻译后操纵者之间复杂的相互作用。
Bacterial effectors are potent manipulators of host signaling pathways. The marine bacterium Vibrio parahaemolyticus (V. para), delivers effectors into host cells through two type three secretion systems (T3SS). The ubiquitous T3SS1 is vital for V. para survival in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts. Although the natural host is undefined, T3SS1 effectors attack highly conserved cellular processes and pathways to orchestrate non-apoptotic cell death. Much is known about how T3SS1 effectors function in isolation, but we wanted to understand how their concerted action globally affects host cell signaling. To assess the host response to T3SS1, we compared gene expression changes over time in primary fibroblasts infected with V. para that have a functional T3SS1 (T3SS1+) to those in cells infected with V. para lacking T3SS1 (T3SS1−). Overall, the host transcriptional response to both T3SS1+ and T3SS1− V. para was rapid, robust, and temporally dynamic. T3SS1 re-wired host gene expression by specifically altering the expression of 398 genes. Although T3SS1 effectors target host cells at the posttranslational level to cause cytotoxicity, network analysis indicated that V. para T3SS1 also precipitates a host transcriptional response that initially activates cell survival and represses cell death networks. The increased expression of several key pro-survival transcripts mediated by T3SS1 was dependent on a host signaling pathway that is silenced later in infection by the posttranslational action of T3SS1. Taken together, our analysis reveals a complex interplay between roles of T3SS1 as both a transcriptional and posttranslational manipulator of host cell signaling.
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影响因子：
3.6
作者：
Burdette DL;Seemann J;Orth K
通讯作者：
Orth K
III型弧菌溶血性纤维溶血系统中的结构和调节突变对毒力显示出可变的影响。
影响因子：
2.1
作者：
Calder T;de Souza Santos M;Attah V;Klimko J;Fernandez J;Salomon D;Krachler AM;Orth K
通讯作者：
Orth K
DOI：
10.1016/j.bbrc.2013.07.006
发表时间：
2013-08-23
影响因子：
3.1
作者：
Kirkby, Nicholas S.;Zaiss, Anne K.;Wright, William R.;Jiao, Jing;Chan, Melissa V.;Warner, Timothy D.;Herschman, Harvey R.;Mitchell, Jane A.
通讯作者：
Mitchell, Jane A.
影响因子：
6.4
作者：
Daniels, NA;MacKinnon, L;Slutsker, L
通讯作者：
Slutsker, L
影响因子：
3.1
作者：
Abdel-Latif, MMM;Windle, HJ;Kelleher, D
通讯作者：
Kelleher, D