GENETIC-RELATIONSHIP BETWEEN SOXRS AND MAR LOCI IN PROMOTING MULTIPLEANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI

Multiple antibiotic resistance in Escherichia coli has typically been associated,vith mutations at the mar locus, located at 34 min on the E . coli chromosome. A new mutant, marC, isolated on the basis of a Mar phenotype but which maps to the soxRS (encoding the regulators of the superoxide stress response) locus located at 92 min, is described here . This mutant shares several features with a known constitutive allele of the soxRS gene, prompting the conclusion that it is a highly activ e allele of this gene. The marC mutation has thus been given the desig nation soxR201. This new mutant was used to examine the relationship b etween the mar and son loci in promoting antibiotic resistance. The re sults of these studies indicate that full antibiotic resistance result ing from the soxR201 mutation is partially dependent on an intact mar Locus and is associated with an increase in the steady-state level of mar-specific mRNA. In addition, paraquat treatment of wild-type cells is shown to increase the level of antibiotic resistance in a dose-depe ndent manner that requires an intact soxRS locus. Conversely, overexpr ession of MarA from a multicopy plasmid results in weak activation of a superoxide stress response target gene. These findings are consisten t with a model in which the regulatory factors encoded by the marA and soxS genes control the expression of overlapping sets of target genes , with MarA preferentially acting on targets involved with antibiotic resistance and SoxS directed primarily towards components of the super oxide stress response. Furthermore, compounds frequently used to induc e the superoxide stress response, including paraquat, menadione, and p henazine methosulfate, differ with respect to the amount of protection provided against them by the antibiotic resistance response.