Sub-operon promoter arrangement of disA facilitates c-di-AMP homeostasis and selective stress responses in M. smegmatis

Abstract

AbstractBacterial 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 M. smegmatis. We have discovered that, although c-di-AMP synthesis gene disA exists in a multi-gene operon; a sub-operon promoter arrangement plays a key role under various stress conditions, keeping its dual function property intact. Further, we learned that c-di-AMP plays a role in the autoregulation of the disA promoter to limit intracellular c-di-AMP concentration. We also identified an alternate start codon within the disA gene which can lead to the synthesis of truncated DisA protein at times using an independent stress-inducible promoter. All in all, 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.