Effects of Carbohydrate Source on Genetic Competence in Streptococcus mutans
Effects of Carbohydrate Source on Genetic Competence in Streptococcus mutans
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DOI：
10.1128/aem.01205-16
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发表时间：
2016-06
影响因子：
4.4
通讯作者：
Zachary D. Moye;Minjun Son;Ariana E Rosa-Alberty;L. Zeng;Sang-Joon Ahn;S. Hagen;R. Burne
中科院分区：
文献类型：
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作者：
Zachary D. Moye;Minjun Son;Ariana E Rosa-Alberty;L. Zeng;Sang-Joon Ahn;S. Hagen;R. Burne
摘要碳水化合物的内化和分解代谢能力是龋齿病原体持续存在并导致疾病的必要条件。变形链球菌是一种与人类龋齿密切相关的生物体，其许多毒力相关属性的表达受到控制遗传能力的肽信号通路的影响。在这里，我们展示了感受态信号传导的效率和碳水化合物来源之间的关系。与在葡萄糖上生长的细胞相比，在以果糖、麦芽糖、蔗糖或海藻糖作为主要碳水化合物源生长的细胞中观察到在暴露于感受态刺激肽（CSP）后，comX、comS和comYA的启动子的活性显著增加。然而，只有在海藻糖或蔗糖存在下生长的细胞显示转化频率显著增加。值得注意的是，即使是低浓度的这些碳水化合物在过量的葡萄糖的存在下，可以增强comX的表达，编码的能力所需的西格玛因子，和能力的影响是依赖于同源糖：磷酸转移酶通透酶的每种碳水化合物。使用绿色荧光蛋白（GFP）报告融合，我们观察到，在果糖或海藻糖中的生长导致更大比例的人口激活表达的comX和comS，编码前体的comX诱导肽（XIP），添加CSP后，比在葡萄糖中的生长。因此，碳水化合物的来源显著影响调节亚群对CSP反应的随机行为，这可以诱导S.变种人重要性调节变异链球菌遗传能力发展的信号通路与生物体的致病潜力密切相关，影响生物膜形成、应激耐受性和已知毒力决定因子的表达。感受态刺激肽（CSP）诱导感受态主调节因子ComX基因发生在细胞亚群中。在这里，我们表明，人类饮食中常见的某些碳水化合物增强了CSP激活comX转录的能力，并且这些碳水化合物的一个子集刺激了向主管状态的进展。这些作用需要每种糖的同源糖：磷酸转移酶。有趣的是，单细胞分析表明，增加玉米基因表达的碳水化合物是通过增加对CSP有反应的细胞比例来实现的。开发了一个数学模型来解释碳水化合物如何通过ComRS途径和ComX稳定性来调节系统中的CO2行为。
ABSTRACT The capacity to internalize and catabolize carbohydrates is essential for dental caries pathogens to persist and cause disease. The expression of many virulence-related attributes by Streptococcus mutans, an organism strongly associated with human dental caries, is influenced by the peptide signaling pathways that control genetic competence. Here, we demonstrate a relationship between the efficiency of competence signaling and carbohydrate source. A significant increase in the activity of the promoters for comX, comS, and comYA after exposure to competence-stimulating peptide (CSP) was observed in cells growing on fructose, maltose, sucrose, or trehalose as the primary carbohydrate source, compared to cells growing on glucose. However, only cells grown in the presence of trehalose or sucrose displayed a significant increase in transformation frequency. Notably, even low concentrations of these carbohydrates in the presence of excess glucose could enhance the expression of comX, encoding a sigma factor needed for competence, and the effects on competence were dependent on the cognate sugar:phosphotransferase permease for each carbohydrate. Using green fluorescent protein (GFP) reporter fusions, we observed that growth in fructose or trehalose resulted in a greater proportion of the population activating expression of comX and comS, encoding the precursor of comX-inducing peptide (XIP), after addition of CSP, than growth in glucose. Thus, the source of carbohydrate significantly impacts the stochastic behaviors that regulate subpopulation responses to CSP, which can induce competence in S. mutans. IMPORTANCE The signaling pathways that regulate development of genetic competence in Streptococcus mutans are intimately intertwined with the pathogenic potential of the organism, impacting biofilm formation, stress tolerance, and expression of known virulence determinants. Induction of the gene for the master regulator of competence, ComX, by competence-stimulating peptide (CSP) occurs in a subpopulation of cells. Here, we show that certain carbohydrates that are common in the human diet enhance the ability of CSP to activate transcription of comX and that a subset of these carbohydrates stimulates progression to the competent state. The cognate sugar:phosphotransferase permeases for each sugar are needed for these effects. Interestingly, single-cell analysis shows that the carbohydrates that increase com gene expression do so by enhancing the proportion of cells that respond to CSP. A mathematical model is developed to explain how carbohydrates modulate bistable behavior in the system via the ComRS pathway and ComX stability.