Cyclic di-GMP Signaling in Bacillus subtilis

The ubiquitous second messenger bis-(3′-5′)-cyclic diguanosine monophosphate (cyclic di-GMP) plays a key role in regulating the transition from motility to sessility in bacteria. While cyclic di-GMP regulation is well studied in a number of Gram-negative bacteria, the physiological role of cyclic di-GMP in Gram-positive organisms is less characterized. Bacillus subtilis is an important model Gram-positive organism that differentiates into distinct subpopulations, such as motile, competent, biofilm-forming, and sporulating cells. Several recent investigations have begun to address how cyclic di-GMP regulates some of these cellular outcomes. The B. subtilis genome encodes three diguanylate cyclases (DGCs) and one phosphodiesterase (PDE), whose respective activities were shown to affect motility. Additionally, three cyclic di-GMP receptors, MotI, YdaK, and YkuI have been discovered. MotI is a PilZ domain protein that inhibits motility by interacting with the MotA stator element of the flagellar apparatus, revealing a direct relationship between cyclic di-GMP signaling and flagellar motility. YdaK was shown to regulate production of a novel exopolysaccharide, suggesting cyclic di-GMP may also impact biofilm formation. YkuI’s involvement in phenotypic regulation has not yet been ascertained, although a connection with zinc homeostasis has been suggested. This review will discuss the discoveries that have led to our current understanding of cyclic di-GMP signaling and regulation in B. subtilis. Outstanding questions and comparison of cyclic di-GMP regulation in other Gram-positive organisms will also be addressed.