Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.
Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.
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DOI：
10.1016/j.cub.2015.11.056
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发表时间：
2016-01-25
期刊：
影响因子：
--
通讯作者：
Rahme LG
中科院分区：
文献类型：
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作者：
Hazan R;Que YA;Maura D;Strobel B;Majcherczyk PA;Hopper LR;Wilbur DJ;Hreha TN;Barquera B;Rahme LG
细菌程序性细胞死亡和群体感应是原核生物群体行为的直接例子，其中细胞协调其行为，像一个有机体一样协同运作，以造福整个培养物。我们在此证明了 2-n-庚基-4-羟基喹啉-N-氧化物 (HQNO) 是一种铜绿假单胞菌群体感应调节的低分子量分泌分子，并通过自扰动细胞色素 bc1 复合物的电子转移反应来触发自溶。 HQNO 通过破坏细胞色素 bc1 复合体上呼吸链的电子流，导致 O2 的还原当量泄漏，从而将通常传递给细胞色素 c 的电子直接提供给 O2，从而诱导特定的自中毒。随后大量产生的活性氧 (ROS) 会降低膜电位并破坏膜完整性，导致细菌细胞自溶和 DNA 释放。 DNA 随后促进生物膜形成并增加对 β-内酰胺的抗生素耐受性，表明 HQNO 依赖性细胞自溶对细菌群体有利。这些数据都确定了一种新的程序性细胞死亡系统，以及 HQNO 作为生物膜形成和抗生素耐受性的关键诱导剂的新作用。这个新发现的途径表明与真核细胞凋亡的最初线粒体介导的步骤具有有趣的机制相似性。
Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum sensing -regulated low-molecular-weight excreted molecule, and triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data both identify a new programmed cell death system, and a novel role for HQNO as a critical-inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.