GacS

GacS is a sensor histidine kinase that forms part of the GacS/GacA two-component regulatory system found in many Gram-negative bacteria, most notably Pseudomonas species. The core components are GacS, a membrane-bound sensor kinase, GacA, a cytoplasmic response regulator, and the small RNAs RsmY and RsmZ, whose expression is controlled by GacA. GacS detects environmental cues such as nutrient status, surface contact, or plant-related signals, and autophosphorylates at a conserved histidine residue. The phosphate is then transferred to GacA on a conserved aspartate, activating GacA to promote transcription of rsmY and rsmZ.

The resulting RsmY and RsmZ small RNAs bind and sequester the RNA-binding proteins RsmA and RsmN, preventing them from repressing their target mRNAs. This post-transcriptional regulation shifts gene expression toward traits such as exoproduct production, secretion systems, motility, biofilm formation, and interactions with quorum-sensing networks. In effect, the GacS/GacA pathway acts as a global switch that integrates environmental signals to coordinate lifestyle decisions between acute virulence and chronic behaviors.

Regulation of GacS/GacA is modulated by accessory factors, including RetS, which inhibits GacS signaling, and LadS, which promotes signaling through the pathway. The GacS/GacA system is conserved across many Pseudomonas species and related bacteria and plays a central role in pathogenicity, biocontrol, and ecological interactions.