Introduction of the virulence plasmid, ColV, I-K94, into 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°C; the sensitivity of ColV, I-JC94 organisms grown at 25°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°C or 37°C or the ColV, I-K94 derivative grown at 25°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 Col V-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.


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