Thiol-based switch mechanism of virulence regulator AphB modulates oxidative stress response in Vibrio cholerae.
Thiol-based switch mechanism of virulence regulator AphB modulates oxidative stress response in Vibrio cholerae.
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DOI：
10.1111/mmi.13524
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发表时间：
2016-12
影响因子：
3.6
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Liu Z;Wang H;Zhou Z;Sheng Y;Naseer N;Kan B;Zhu J
细菌病原体显示出多功能的基因表达，以适应不断变化的环境。例如，霍乱弧菌，霍乱的病原体，利用不同的遗传程序来对抗水生环境中或宿主感染期间的活性氧（ROS）。我们以前报道过霍乱弧菌中的毒力激活因子AphB参与了ROS抗性。在这里，通过进行遗传筛选，我们表明，AphB抑制ROS抗性基因ohrA，这也是由另一个调节器，OhrR抑制。还原形式的AphB和OhrR直接结合到ohrA启动子并抑制其表达，而有机氢过氧化物如氢过氧化枯烯（CHP）使AphB和OhrR失活。OhrA对于霍乱弧菌成年小鼠定殖是至关重要的，但当小鼠用抗氧化剂处理时，OhrA被抑制。此外，类似于我们以前的发现，AphB和OhrR表现出不同的还原率在从好氧到缺氧的环境中的转变，我们发现，AphB也氧化更慢，比OhrR下过氧化氢应力或暴露于氧气。这种差异调节优化了ohrA的表达，并有助于霍乱弧菌在含有不同水平ROS的各种环境小生境中存活的能力。像许多其他细菌一样，人类病原体霍乱弧菌能够对抗活性氧（ROS）。我们发现霍乱弧菌毒力调节因子AphB与有机氢过氧化物抗性调节因子OhrR共同作用，通过OhrA调节ROS抗性。AphB和OhrR对氧化还原电位的反应不同，因此它们可以微调ohrA的表达，以更好地适应各种环境生态位。
Bacterial pathogens display versatile gene expression to adapt to changing surroundings. For example, Vibrio cholerae, the causative agent of cholera, utilizes distinct genetic programs to combat reactive oxygen species (ROS) in aquatic environments or during host infection. We previously reported that the virulence activator AphB in V. cholerae is involved in ROS resistance. Here by performing a genetic screen, we show that AphB represses ROS resistance gene ohrA, which is also repressed by another regulator, OhrR. Reduced forms of both AphB and OhrR directly bind to the ohrA promoter and repress its expression, whereas organic hydroperoxides such as cumene hydroperoxide (CHP) deactivate AphB and OhrR. OhrA is critical for V. cholerae adult mouse colonization but is dispensable when the mice are treated with antioxidants. Furthermore, similar to our previous finding that AphB and OhrR exhibit different reduction rates during the shift from oxic to anoxic environments, we found that AphB is also oxidized more slowly than OhrR under peroxide stress or exposure to oxygen. This differential regulation optimizes the expression of ohrA and contributes to V. cholerae's ability to survive in a variety of environmental niches that contain different levels of ROS. Like many other bacteria, the human pathogen Vibrio cholerae is able to combat reactive oxygen species (ROS). We found that V. cholerae virulence regulator AphB works together with organic hydroperoxide resistance regulator OhrR to regulate ROS resistance through OhrA. AphB and OhrR respond to redox potentials differently so that they fine-tune ohrA expression to better adapt various environmental niches.
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影响因子：
3.2
作者：
Kovacikova, Gabriela;Lin, Wei;Skorupski, Karen
通讯作者：
Skorupski, Karen
影响因子：
11.4
作者：
Lesniak, J;Barton, WA;Nikolov, DB
通讯作者：
Nikolov, DB
DOI：
10.1016/j.bbagen.2003.10.016
发表时间：
2004-01-05
影响因子：
3
作者：
Bhattacharyya, S;Ghosh, S;Majumdar, S
通讯作者：
Majumdar, S
影响因子：
2.6
作者：
Sukchawalit, R;Prapagdee, B;Mongkolsuk, S
通讯作者：
Mongkolsuk, S
影响因子：
30.3
作者：
Fang FC;Frawley ER;Tapscott T;Vázquez-Torres A
通讯作者：
Vázquez-Torres A