Bacterial second messenger signaling often plays an important role in cellular physiology. In this study, we have attempted to understand how c-di-AMP synthesis and degradation are transcriptionally regulated in Mycobacterium smegmatis. We found that although a c-di-AMP synthesis gene, disA, exists in a multi-gene operon, a sub-operon promoter arrangement facilitates disA gene expression under normal conditions to maintain intracellular c-di-AMP concentration and is induced further during certain stress adaptations. Individual gene-specific promoters also play a key role under various genotoxic stress conditions to shut down c-di-AMP synthesis, which could otherwise be detrimental for cells. Further, we learned that a high c-di-AMP concentration plays a role in the autoregulation of the disA promoter to limit intracellular c-di-AMP concentration. This study was helpful to understand how c-di-AMP synthesis is regulated under normal and stress conditions linked to its physiological relevance in M. smegmatis.

细菌第二信使信号传导通常在细胞生理学中发挥重要作用。在这项研究中，我们试图了解耻垢分枝杆菌中 c-di-AMP 合成和降解是如何进行转录调控的。我们发现，虽然 c-di-AMP 合成基因disA存在于多基因操纵子中，但亚操纵子启动子排列有利于disA正常条件下基因表达以维持细胞内 c-di-AMP 浓度，并在某些应激适应过程中进一步诱导。单个基因特异性启动子在各种基因毒性应激条件下也发挥关键作用，以关闭 c-di-AMP 合成，否则可能对细胞有害。此外，我们了解到高 c-di-AMP 浓度在disA启动子的自动调节中发挥作用，以限制细胞内 c-di-AMP 浓度。这项研究有助于了解在耻垢分枝杆菌中，c-di-AMP 合成在正常和应激条件下如何受到调节，及其生理相关性。