Potassium glutamate accumulates upon hyper-osmotic shock and serves as a temporary osmoprotectant. This salt leads to transcriptional activation of sets of genes that allow the cell to achieve long-term adaptation to high osmolarity. The current experiments show that potassium glutamate also acts as an inhibitor of bulk cellular transcription. It can do so independent of the involvement of macromolecular repressors or activators by virtue of its ability to directly inhibit RNA polymerase binding to ribosomal promoters. Thus, potassium glutamate mediates a global transcription switch by acting differentially on RNA polymerase at sets of genomic promoters that differ in their built-in direct response to this salt.