Discovery of the Second Messenger Cyclic di-GMP

The nearly ubiquitous bacterial second messenger cyclic di-GMP is involved in a multitude of fundamental physiological processes such as sessility/motility transition and the switch between the acute and chronic infection status, combined with cell cycle control. The discovery of cyclic di-GMP, though, has been an example par excellence of scientific serendipity. We recapitulate here its years-long discovery process as an activator of the cellulose synthase of the environmental bacterium Komagataeibacter xylinus and its consequences for follow-up research. Indeed, the discovery of cyclic di-GMP as a ubiquitous second messenger contributed to the change in perception of bacteria as simple unicellular organisms just randomly building-up multicellular communities. Subsequently, cyclic di-GMP also paved the way to the identification of other pro- and eukaryotic cyclic dinucleotide second messengers.