Expression of a particular set of exported protein genes (ompF, ompC, phoA, and malE) can be specifically altered in three ways: variation in the osmotic strength of the growth medium, mutations in the regulatory locus envZ, or treatment with sublethal concentrations of the local anesthetic procaine. To clarify relationships among these factors in the regulation of transcription, expression of the affected genes was compared in envZ+ and envZ22(Am) mutant strains grown in media of differing osmolarities with and without procaine. Loss of the envZ product resulted in complete resistance of gene expression to procaine, supporting the hypothesis that envZ mediates procaine inhibition. The specific activity of the phoA product, alkaline phosphatase, was elevated in envZ22 mutant strains, while the amounts of both the OmpC and OmpF porins were reduced. Osmotic control of phoA and ompC was retained in the absence of envZ function, but osmoregulation of ompF was lost. Therefore, the envZ product is somehow involved in the complex regulation of all four target genes, but is not solely responsible for osmoregulation
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