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Tracking the homeostasis of second messenger cyclic-di-GMP in bacteria


Cyclic-di-GMP (c-di-GMP) is an important second messenger in bacteria which regulates the bacterial transition from motile to sessile phase and also plays a major role in processes such as cell division, exopolysaccharide synthesis, and biofilm formation. Due to its crucial role in dictating the bacterial phenotype, the synthesis and hydrolysis of c-di-GMP is tightly regulated via multiple mechanisms. Perturbing the c-di-GMP homeostasis affects bacterial growth and survival, so it is necessary to understand the underlying mechanisms related to c-di-GMP metabolism. Most techniques used for estimating the c-di-GMP concentration lack single-cell resolution and do not provide information about any heterogeneous distribution of c-di-GMP inside cells. In this review, we briefly discuss how the activity of c-di-GMP metabolising enzymes, particularly bifunctional proteins, is modulated to maintain c-di-GMP homeostasis. We further highlight how fluorescence-based methods aid in understanding the spatiotemporal regulation of c-di-GMP signalling. Finally, we discuss the blind spots in our understanding of second messenger signalling and outline how they can be addressed in the future.

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AP and SYN acknowledge DST for their fellowship.


This study is funded by the Department of Science and Technology (DST), Government of India, and IISc

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Correspondence to Anushya Petchiappan.

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Petchiappan, A., Naik, S.Y. & Chatterji, D. Tracking the homeostasis of second messenger cyclic-di-GMP in bacteria. Biophys Rev (2020). https://doi.org/10.1007/s12551-020-00636-1

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  • C-di-GMP
  • Second messenger
  • Biofilm
  • Biosensor
  • FRET
  • Riboswitch