dksA

DksA is a transcription factor in bacteria that modulates RNA polymerase activity during the stringent response. It is encoded by the dksA gene and is conserved across many bacterial lineages, including Escherichia coli and related species. The DksA protein is relatively small, featuring a coiled-coil domain that extends into the RNA polymerase secondary channel, where an apex region contains acidic residues implicated in its regulatory action.

Mechanistically, DksA acts in concert with the alarmone ppGpp to reshape transcription initiation at various promoters. The DksA-ppGpp complex can repress transcription from rRNA and ribosomal protein operons, thereby limiting protein synthesis during nutrient limitation, while promoting transcription of genes involved in amino acid biosynthesis and other stress responses. The exact effect is promoter-dependent and influenced by growth conditions, RNA polymerase isoforms, and the cellular ppGpp level.

Physiological role, and relevance, include its central place in coordinating growth rate with nutrient availability. By tuning transcription, DksA helps bacteria adapt to starvation and other stresses, and it can influence virulence traits and antibiotic susceptibility in certain pathogens. Genetic disruption of dksA often leads to altered growth, stress sensitivity, and changes in global transcription patterns.

Evolution and classification place DksA in the DksA/TraR family of RNA polymerase-binding transcription factors. Its activity is tightly linked to the stringent response and ppGpp signaling, making it a key node in bacterial transcriptional regulation.