Increased sensitivity to erythromycin in Escherichia coli associated with the presence of the ColV,I-K94 virulence plasmid.

Introduction of the virulence plasmid, ColV,I-K94, into Escherichia coli strains led to increased sensitivity to erythromycin. This was the result of increased passage of antibiotic into ColV,I-K94+ organisms because the plasmid effect was abolished in bacteria which had been made permeable by chemical treatment. Full sensitivity in ColV+ strains appears to depend on the simultaneous presence of transfer and colicin components. Increased erythromycin sensitivity associated with the plasmid was demonstrated in organisms grown at 37 degrees C; the sensitivity of ColV,I-K94+ organisms grown at 25 degrees C was similar to that of the parent strain. Added Mg++ or Ca++ ions reversed erythromycin inhibition in strains with the basal level of sensitivity (i.e., the Col- parent grown at 25 degrees C or 37 degrees C or the ColV,I-K94+ derivative grown at 25 degrees C) and in those with the plasmid-associated increase in sensitivity. Addition of phosphate or EDTA to broth increased erythromycin sensitivity in Col- and ColV,I-K94+ strains although the latter was affected most. Erythromycin was more inhibitory at pH 8.5 than at pH 7.4. This enhanced activity was more marked against the ColV,I-K94+ strain than against the Col- strain. The effects of growth in phosphate-containing medium and at alkaline pH were partially additive. We suggest that ColV,I-K94+ strains may be sensitive to erythromycin because ColV-specified proteins are extruded by a process of "self-promoted transfer" and that the effects of these proteins on the lipopolysaccharide component of the outer membrane facilitates antibiotic influx.