Homeostatic interplay between bacterial cell-cell signaling and iron in virulence.
Homeostatic interplay between bacterial cell-cell signaling and iron in virulence.
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DOI：
10.1371/journal.ppat.1000810
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发表时间：
2010-03-12
期刊：
影响因子：
6.7
通讯作者：
Rahme LG
中科院分区：
文献类型：
--
作者：
Hazan R;He J;Xiao G;Dekimpe V;Apidianakis Y;Lesic B;Astrakas C;Déziel E;Lépine F;Rahme LG
病原菌利用相互连接的多层调控网络，如群体感应(Quorum Sensing，QS)网络来感知和响应环境提示以及内外细菌细胞信号，从而适应和利用目标宿主。尽管在理解QS监管方面已经取得了许多进展，但关于这些输入如何在多层QS监管网络中整合和处理的知之甚少。在这里，我们报告了铜绿假单胞菌4-羟基-2-烷基喹啉(HAQS)MvfR调节网络的检测及其与QS酰基-高丝氨酸-内酯(AHL)RhlR网络的相互作用。这项工作的目的是以范例的方式阐明多层调节QS电路、它们的信号分子和它们响应的环境线索之间的复杂关系。我们的发现揭示了正负稳态调节环，通过细胞-细胞信号分子PQS和HHQ的多层依赖的稳态调节，以及这些分子与铁的相互作用，微调MvfR调节子。我们发现，MvfR调节子组件PqsE是协调这种内稳态调节的关键介质，并与RhlR合作建立与QS rhLR系统的连接。我们的结果表明，铜绿假单胞菌至少部分地通过这种多层相互作用来调节其毒力反应的强度。我们的发现强调了在控制毒力基因表达中，通过细胞-细胞信号分子和环境线索平衡QS系统内部和之间竞争的动态平衡相互作用的重要性。对这种复杂关系的微调的阐明为这些系统的调节提供了新的见解，并可能为旨在限制由铜绿假单胞菌和相关人类病原体引起的感染的策略提供参考。细菌细胞可以就其周围环境相互交流。这种信息可以是自我分泌的小分子，作为激活或抑制基因表达的信号。铜绿假单胞菌是一种环境细菌，可以感染从植物到人类的各种生物。我们的结果表明，该病原菌使用两个高度敏感的网络，即MvfR和LasR/RhlR途径，通过滴定小分子HHQ和PQS的浓度来调节其毒力功能，这种方式取决于铁的存在或不存在。通过负反馈和正反馈循环，这种细菌处理信号信息来调节其毒力功能，并动态平衡激活MvfR毒力网络所需的小分子的产生。我们的研究揭示了维持动态平衡细菌毒力反应的聚合复杂网络。
Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens. Bacterial cells can communicate with one another about their surrounding environment. This information can be in the form of small self-secreted molecules acting as signals to activate or inhibit the expression of genes. Pseudomonas aeruginosa is an environmental bacterium that infects diverse organisms from plants to humans. Our results show that this pathogen uses two highly sensitive networks, namely MvfR and LasR/RhlR pathways, to modulate its virulence functions by titrating the concentration of the small molecules HHQ and PQS in a manner that depends upon the presence or absence of iron. Via negative and positive feedback loops, this bacterium processes the signaled information to regulate its virulence functions and homeostatically balance the production of the small molecules required for the activation of the MvfR virulence network. Our study sheds light on paradigmatic complex networks that maintain a homeostatic bacterial virulence response.
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