The Evanescent GacS Signal

The GacS histidine kinase is the membrane sensor of the major upstream two-component system of the regulatory Gac/Rsm signal transduction pathway. This pathway governs the expression of a wide range of genes in pseudomonads and controls bacterial fitness and motility, tolerance to stress, biofilm formation, and virulence or plant protection. Despite the importance of these roles, the ligands binding to the sensor domain of GacS remain unknown, and their identification is an exciting challenge in this domain. At high population densities, the GacS signal triggers a switch from primary to secondary metabolism and a change in bacterial lifestyle. It has been suggested, based on these observations, that the GacS signal is a marker of the emergence of nutritional stress and competition. Biochemical investigations have yet to characterize the GacS signal fully. However, they portray this cue as a low-molecular weight, relatively simple and moderately apolar metabolite possibly resembling, but nevertheless different, from the aliphatic organic acids acting as quorum-sensing signaling molecules in other Proteobacteria. Significant progress in the development of metabolomic tools and new databases dedicated to Pseudomonas metabolism should help to unlock some of the last remaining secrets of GacS induction, making it possible to control the Gac/Rsm pathway.