Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation.
Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation.
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DOI：
10.3389/fmicb.2016.00804
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发表时间：
2016
影响因子：
5.2
通讯作者：
Stülke J
中科院分区：
文献类型：
--
作者：
Gundlach J;Rath H;Herzberg C;Mäder U;Stülke J
革兰氏阳性模式生物枯草芽孢杆菌产生必需的第二信使信号核苷酸环状二AMP。在B。枯草杆菌和其他细菌中，c-di-AMP涉及多种功能，例如控制代谢、细胞分裂和细胞壁合成以及钾转运。为了加强我们对这种第二信使的多种功能的理解，我们通过转录组分析研究了c-di-AMP积累在全球水平上的后果。C-di-AMP积累影响了约700个基因的表达，其中包括生物膜形成所需的两个主要操纵子。这两个操纵子的表达在实验室和非驯化的菌株后，积累的c-di-AMP严重减少。在极好的一致性中，相应的菌株不能形成复杂的菌落。在B。在枯草芽孢杆菌中，转录因子SinR通过与生物膜基因的启动子区结合导致转录抑制来控制生物膜基因的表达。即使在高细胞内c-di-AMP浓度下，sinR基因的失活也恢复了生物膜的形成，这表明第二信使在信号转导途径中在SinR的上游起作用。由于c-di-AMP积累不影响细胞内的SinR水平，我们得出结论，核苷酸影响SinR的活性。
The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR.