An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes
An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes
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DOI：
10.1111/1462-2920.15008
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发表时间：
2020-04-21
影响因子：
5.1
通讯作者：
Commichau, Fabian M.
中科院分区：
文献类型：
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作者：
Gibhardt, Johannes;Heidemann, Jana L.;Commichau, Fabian M.
第二信使环二-AMP（c-di-AMP）是许多细菌生长所必需的，因为它控制着渗透压平衡。c-di-AMP可调节某些细菌钾吸收系统的合成，也可直接抑制和激活钾的输入和输出系统。因此，c-di-AMP的产生和降解必须根据环境渗透压进行严格调节。革兰氏阳性病原体单核细胞增生李斯特菌依赖于膜结合的二腺苷酸环化酶CdaA来产生c-di-AMP，并利用两种磷酸二酯酶降解核苷酸。虽然生产和降解二核苷酸的酶已被合理地很好地检查，但c-di-AMP生产的调节尚未得到很好的理解。在这里，我们表明，胞质外调节CdaR通过其跨膜螺旋与CdaA相互作用，以调节c-di-AMP的生产。此外，我们表明，磷酸葡糖胺的GlmM与CdaA形成复合物，并在体外抑制二腺苷酸环化酶的活性。我们还发现GlmM抑制L.当细菌遇到渗透胁迫时，单核细胞增多症。因此，GlmM是体内控制CdaA活性的主要因素。GlmM可以被归为兼职蛋白类，因为它在代谢中具有活性，并根据环境渗透压调节细胞膨压。
The second messenger cyclic di-AMP (c-di-AMP) is essential for growth of many bacteria because it controls osmolyte homeostasis. c-di-AMP can regulate the synthesis of potassium uptake systems in some bacteria and it also directly inhibits and activates potassium import and export systems, respectively. Therefore, c-di-AMP production and degradation have to be tightly regulated depending on the environmental osmolarity. The Gram-positive pathogen Listeria monocytogenes relies on the membrane-bound diadenylate cyclase CdaA for c-di-AMP production and degrades the nucleotide with two phosphodiesterases. While the enzymes producing and degrading the dinucleotide have been reasonably well examined, the regulation of c-di-AMP production is not well understood yet. Here we demonstrate that the extracytoplasmic regulator CdaR interacts with CdaA via its transmembrane helix to modulate c-di-AMP production. Moreover, we show that the phosphoglucosamine mutase GlmM forms a complex with CdaA and inhibits the diadenylate cyclase activity in vitro. We also found that GlmM inhibits c-di-AMP production in L. monocytogenes when the bacteria encounter osmotic stress. Thus, GlmM is the major factor controlling the activity of CdaA in vivo. GlmM can be assigned to the class of moonlighting proteins because it is active in metabolism and adjusts the cellular turgor depending on environmental osmolarity.