The mechanisms whereby salicylates and some related compounds alter the antibiotic resistances of E. coli have been further elucidated. In collaboration with S. Levy, we have found that salicylate-treated cells are similar to certain marA mutants. Salicylate-treated cells are multiply antibiotic resistant, have outer membranes with decreased permeability to cephalosporins, have reduced levels of the outer membrane protein OmpF, and have increased levels of micF mRNA which is antisense to and which down- regulates ompF translation. mara mutants overexpress three adjacent ORFs (in the absence of salicylate) and this, somehow, leads to the same phenotype found for salicylate-treated cells. We have now shown that salicylate stimulates the expression of the marA operon, whether normal or mutant. Thus, the similarities between salicylate-treated cells and marA mutants is likely to be due to this common affect on marA expression. An effect of salicylate (and the non-acidic, salicyl alcohol) that is not observed with mutants is that they increase E. coli's sensitivity to various positively charged antimicrobial aminoglycosides, bleomycin and Cd(++). Two uptake systems for Cd were observed in untreated cells. Treatment with salicylate or salicyl alcohol increased the Vmax but did not change the Km of these systems. The clear correlation between increased sensitivity and increased uptake of Cd(++) suggests that the mechanism of salicylate action in this case is to increase the uptake of certain cations.
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