R Factors-Determined Changes in Permeability of E. Coli Towards Rifampicin and other Antibiotics

Distribution in Nature of R factors that Increase Susceptibility to Rifampin of rif-r Mutants in Escherichia coli

“…Thus they behaved like previously studied R factors of our collection of strains (3,4). We consider the lowered plating effi'ciency of the rif-r R+ recombinants to be due to decrease in rifampin resistance.…”

“…This might render a fraction of the conjugants susceptible to the antibiotic that is added to select for the R factor. This explanation, however, can be rejected since clones of AJ4 (R163) grown in the absence of the antibiotic selective for the R factor have a reduced minimal inhibitory concentration for rifampin in broth as compared with clones of AJ4 R- (3,4). (ii) Another hypothesis made unlikely by the studies of individual clones is that the reduced plating efficiency is due to the synergistic inhibition by the two antibiotics.…”

“…We reported also that such rif-r mutants, when R+, are more susceptible to erythromycin, to actinomycin D, and to some rifamycin derivatives which, because they possess a free carboxyl group on the side chain of the rifamycin molecule, do not penetrate efficiently into gram-negative bacteria (3). Since the molecular targets of erythromycin, actinomycin D, and rifamycins are different, and since the ribonucleic acid polymerases extracted from isogenic R-and R+ strains are equally susceptible to rifampin, we concluded that R factors increase the permeability of this class of rif-r mutants to these three antibiotics (3,4). This observation (that some R factors among our collection of strains increase the sensitivity of these rif-r mutants to some antibiotics) could become of practical interest if the phenomenon also applies to R factors in natural bacterial populations.…”

“…We isolated 117 gram-negative strains from pathological materials and tested them for presence of R factors transferable to K-12. The 46 strains found to carry R factors were conjugated to strain AJ4, a rif-r mutant belonging to the class of mutants whose susceptibility to rifampin is affected by R factors (3,4), and the susceptibility of the R+ exconjugants was compared with that of the R-AJ4 strain. Since we wanted to work with the same rif-r mutant already used in previous work (3, 4), we were obliged to transfer the R factors in two steps: (i) to a chromosomally resistant auxotroph; and (ii) from the auxotroph to AJ4.…”

On the Mode of Action of the Immunosuppressive Sesquiterpene Ovalicin

“…All these effects including those occurring after a long exposure of the cells to the drug are observed with very low concentrations of the inhibitor. It is important to stress this fact because at higher concentrations hydrophobic drugs such as ovalicin can bind to many different sites in the cell by rather unspecific hydrophobic interactions with the consequence of inhibiting several reactions separately and independently as has been proven for the rifamycins [27,28] or novobiocin and nalidixic acid [29]. At such low concentrations of a drug (100-0.1 nM) as were used in our experiments unspecific binding has not been reported so far for other drugs.…”