Origins of heterogeneity in Streptococcus mutans competence: interpreting an environment-sensitive signaling pathway.
Origins of heterogeneity in Streptococcus mutans competence: interpreting an environment-sensitive signaling pathway.
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DOI：
10.1088/1478-3975/aa546c
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发表时间：
2017-01-27
期刊：
影响因子：
2
通讯作者：
Son M
中科院分区：
文献类型：
--
作者：
Hagen SJ;Son M
细菌病原体依赖于化学信号和环境线索来调节复杂微环境中的致病行为。人类病原体变形链球菌（Streptococcus mutans）采用一种特别复杂的信号传导和传感机制来调节其所处的口腔生物膜中的遗传能力和其他毒力行为。个体S.变形细胞通过整合从其微环境接收的化学和物理信号沿着内源性产生的肽信号来决定进入感受态。在单细胞水平上的研究，使用微流体来控制细胞外环境，提供了对细胞如何处理这些输入以产生复杂且通常是异质的输出的物理见解。环境刺激的细微变化可以极大地改变能力回路的行为。pH的小变化可以打开或关闭群体感应响应，而富含肽的介质似乎将输出从单峰切换到双峰行为。因此，根据环境线索，群体感应电路可以同步整个种群的毒性，或者启动和放大这种行为的异质性。这种复杂的行为中的大部分可以在群体感应系统的框架内理解，该系统既可以作为细胞间的信号传导机制，也可以作为细胞内的噪声双峰开关。
Bacterial pathogens rely on chemical signaling and environmental cues to regulate disease-causing behavior in complex microenvironments. The human pathogen Streptococcus mutans employs a particularly complex signaling and sensing scheme to regulate genetic competence and other virulence behaviors in the oral biofilms it inhabits. Individual S. mutans cells make the decision to enter the competent state by integrating chemical and physical cues received from their microenvironment along with endogenously produced peptide signals. Studies at the single-cell level, using microfluidics to control the extracellular environment, provide physical insight into how the cells process these inputs to generate complex and often heterogeneous outputs. Fine changes in environmental stimuli can dramatically alter the behavior of the competence circuit. Small shifts in pH can switch the quorum sensing response on or off, while peptide-rich media appear to switch the output from a unimodal to a bimodal behavior. Therefore, depending on environmental cues, the quorum sensing circuitry can either synchronize virulence across the population, or initiate and amplify heterogeneity in that behavior. Much of this complex behavior can be understood within the framework of a quorum sensing system that can operate both as an intercellular signaling mechanism and intracellularly as a noisy bimodal switch.