Posttranscriptional repression of Escherichia coli OmpF protein in response to redox stress: positive control of the micF antisense RNA by the soxRS locus

Abstract

The soxRS regulon is a cornerstone of the adaptive defense systems of Escherichia coli against oxidative stress. Unexpectedly, activation of this regulon also enhances bacterial resistance to multiple antibiotics that seem unrelated to oxygen radicals. We previously correlated this multiple antibiotic resistance with a reduced rate of synthesis of the OmpF outer membrane porin that does not affect the OmpC or OmpA porins. Studies presented here, with operon and gene fusions of ompF to lacZ, show that the soxRS-dependent repression of OmpF is achieved posttranscriptionally. We also show posttranscriptional repression of OmpF mediated by the soxQ1 mutation, which maps to the marA locus. These repressions are dependent on the micF gene, which encodes a small RNA partially complementary to the 5' end of the ompF message. Northern (RNA) blotting experiments show that micF transcription is strongly inducible by the superoxide-generating agent paraquat in a manner that depends completely on the soxRS locus. The soxR-constitutive and soxQ1 mutations elevate the expression of micF in the absence of redox stress. However, the antibiotic resistance mediated by a soxR-constitutive mutation was only partially reversed upon deletion of micF. The soxRS regulon therefore includes other components that contribute to general antibiotic resistance, although the relation of this phenotype to oxidative stress remains to be established.