Restricting Fermentative Potential by Proteome Remodeling AN ADAPTIVE STRATEGY EVIDENCED IN BACILLUS CEREUS
Restricting Fermentative Potential by Proteome Remodeling AN ADAPTIVE STRATEGY EVIDENCED IN BACILLUS CEREUS
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DOI：
10.1074/mcp.m111.013102
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发表时间：
2012-06-01
影响因子：
7
通讯作者：
Duport, Catherine
中科院分区：
文献类型：
--
作者：
Clair, Geremy;Armengaud, Jean;Duport, Catherine
致病性兼性厌氧菌在胃肠道的成功定植是其发病机制的关键。胃肠道是一个碳水化合物有限的环境，具有不同的氧气可用性和氧化还原电位（ORP）。病原菌如何能够适应这些不同的条件并在其中生长仍然是一个关键的基本问题。在这里，我们设计了一种系统生物学启发的方法，以确定关键调节因子，使蜡状芽孢杆菌在低ORP缺氧条件下有效地生存和生长，模拟肠腔中遇到的情况。我们使用高通量nanoLC-MS/MS技术评估了蛋白质组组分，重建了主要代谢回路，构建了Delta ohrA和Delta ohrR突变体，并通过新一轮的鸟枪蛋白质组学分析了ohrA和ohrR中断的影响。我们的研究表明，OhrR和OhrA是成功适应B的关键。蜡状芽孢杆菌对胃肠道环境的影响。具体来说，我们证明了B。蜡状芽孢杆菌在低ORP厌氧条件下限制其发酵生长，并通过OhrRA依赖性蛋白质组重塑维持有效的有氧呼吸代谢、运动和应激反应。最后，我们的结果引入了一种新的适应策略，其中兼性厌氧菌更喜欢限制其发酵潜力以获得长期利益。Molecular & Cellular Proteomics 11：10.1074/mcp. M111.013102，1-13，2012.
Pathogenesis hinges on successful colonization of the gastrointestinal (GI) tract by pathogenic facultative anaerobes. The GI tract is a carbohydrate-limited environment with varying oxygen availability and oxidoreduction potential (ORP). How pathogenic bacteria are able to adapt and grow in these varying conditions remains a key fundamental question. Here, we designed a system biology-inspired approach to pinpoint the key regulators allowing Bacillus cereus to survive and grow efficiently under low ORP anoxic conditions mimicking those encountered in the intestinal lumen. We assessed the proteome components using high throughput nanoLC-MS/MS techniques, reconstituted the main metabolic circuits, constructed Delta ohrA and Delta ohrR mutants, and analyzed the impacts of ohrA and ohrR disruptions by a novel round of shotgun proteomics. Our study revealed that OhrR and OhrA are crucial to the successful adaptation of B. cereus to the GI tract environment. Specifically, we showed that B. cereus restricts its fermentative growth under low ORP anaerobiosis and sustains efficient aerobic respiratory metabolism, motility, and stress response via OhrRA-dependent proteome remodeling. Finally, our results introduced a new adaptive strategy where facultative anaerobes prefer to restrict their fermentative potential for a long term benefit. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013102, 1-13, 2012.