HOW IS OSMOTIC REGULATION OF TRANSCRIPTION OF THE ESCHERICHIA-COLI PROU OPERON ACHIEVED - A REVIEW AND A MODEL

The proU operon in enterobacteria encodes a binding-protein-dependent transporter for the active uptake of glycine betaine and L-proline, an d serves an adaptive role during growth of cells in hyperosmolar envir onments. Transcription of proU is induced 400-fold under these conditi ons, but the underlying signal transduction mechanisms are incompletel y understood. Increased DNA supercoiling and activation by potassium g lutamate have each been proposed in alternative models as mediators of proU somoresponsivity. We review here the available experimental data on proU regulation, and in particular the roles for DNA supercoiling, potassium glutamate, histone-like proteins of the bacterial nucleoid, and alternative sigma factors of RNA polymerase in such regulation. W e also propose a new unifying model, in which the pronounced osmotic r egulation of proU expression is achieved through the additive effects of at least three separate mechanisms, each comprised of a cis element [two promoters P1 and P2, and negative-regulatory-element (NRE) downs tream of both promoters] and distinct trans-acting factors that intera ct with it: stationary-phase sigma factor RpoS with P1, nucleoid prote ins HU and IHF with P2, and nucleoid protein H-NS with the NRE. In thi s model, potassium glutamate may activate proU expression through each of the three mechanisms whereas DNA supercoiling has a very limited r ole, if any, in the osmotic induction of proU transcription. We also s uggest that proU may be a virulence gene in the pathogenic enterobacte ria.