Carbohydrate and PepO control bimodality in competence development by Streptococcus mutans
Carbohydrate and PepO control bimodality in competence development by Streptococcus mutans
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DOI：
10.1111/mmi.14367
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发表时间：
2019-08-29
影响因子：
3.6
通讯作者：
Hagen, Stephen J.
中科院分区：
文献类型：
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作者：
Underhill, Simon A. M.;Shields, Robert C.;Hagen, Stephen J.
在变形链球菌中，替代性σ因子ComX控制进入遗传能力。感受态刺激肽（CSP）诱导comX的双峰表达，其中仅一部分群体变得可转化。奇怪的是，comX的双峰性受到生长培养基中的肽和碳水化合物来源的影响。CSP在富含小肽的培养基中诱导了comX的双峰表达，但CSP在缺乏小肽的确定培养基中没有诱导反应。此外，某些糖的生长增加了响应CSP而激活comX的群体的比例。通过调查媒体和comX双峰之间的联系，我们发现两种机制，调节转录的正反馈的ComRS系统，comX双峰起源的证据。我们发现内肽酶PepO抑制ComRS反馈回路，最有可能是通过降解XIP/ComS反馈信号。pepO的缺失消除了comX双峰性，导致在限定和复杂培养基中对CSP的单峰comX响应。我们还发现，CSP刺激的ComRS反馈系统上调comR的碳水化合物源依赖性的方式。我们的数据提供了关于S.变形杆菌调节双峰性，并解释了CSP对感受态诱导的生长介质效应的困惑。
In Streptococcus mutans, the alternative sigma factor ComX controls entry into genetic competence. Competence stimulating peptide (CSP) induces bimodal expression of comX, with only a fraction of the population becoming transformable. Curiously, the bimodality of comX is affected by peptides in the growth medium and by carbohydrate source. CSP elicits bimodal expression of comX in media rich in small peptides, but CSP elicits no response in defined media lacking small peptides. In addition, growth on certain sugars increases the proportion of the population that activates comX in response to CSP. By investigating the connection between media and comX bimodality, we find evidence for two mechanisms that modulate transcriptional positive feedback in the ComRS system, where comX bimodality originates. We find that the endopeptidase PepO suppresses the ComRS feedback loop, most likely by degrading the XIP/ComS feedback signal. Deletion of pepO eliminates comX bimodality, leading to a unimodal comX response to CSP in both defined and complex media. We also find that CSP stimulates the ComRS feedback system by upregulating comR in a carbohydrate source-dependent fashion. Our data provide mechanistic insight into how S. mutans regulates bimodality and explain the puzzle of growth medium effects on competence induction by CSP.