Synergism between streptomycin and penicillin: a proposed mechanism

Brief treatment of growing Escherichia coli with penicillin hastened subsequent killing of these cells by streptomycin. It also hastened the secondary uptake of streptomycin, which represents an increase in the number of freely accessible binding sites. In contrast, brief treatment with streptomycin failed to affect subsequent killing by penicillin. These findings suggest that the synergism of penicillin with streptomycin depends on the damaging effect of penicillin on the cell membrane, which promotes further damage by streptomycin and increases its subsequent access to intracellular sites. Observations on a streptomycin-resistant mutant are also reported.