SUMMARY: The growth characteristics of cultures treated with dihydrostreptomycin and then freed from extracellular antibiotic before growth had completely stopped, were examined. Growth, measured by extinction, proceeded exponentially, but at slower rates for a time, followed by gradual recovery. The degree of slowing of growth rate was a function of the duration of growth in the presence of a given concentration of dihydrostreptomycin. Comparison of viable colony count data and microscopic observation of such treated cultures showed that the majority of individuals in the populations must grow at the lower rates for two-three generations, after which some organisms cease to multiply and the rest recover. The proportion of organisms in treated populations which eventually ceased to grow was also a function of the duration of treatment. The amount of growth (cell synthesis), which had occurred at the time when onset of recovery became measurable, varied inversely with the % inhibition of growth rate. This suggests that recovery was due to some process not inhibited during the phase of inhibited exponential growth. It is concluded that intracellular dihydrostreptomycin consists of an ‘inhibitory fraction’ at the sites of inhibition, and a non-inhibitory ‘pool’ fraction; that the size of the latter varies between different individuals within a population and that transfer from ‘pool’ to inhibitory sites occurs by a process other than equilibration; e.g. that the factors which govern the uptake into these two phases must be, at least partly, independent. It is suggested that the degree of inhibition of growth rate reflects the extent of combination between antibiotic and inhibition sites at the time when extracellular dihydrostreptomycin is removed and no further uptake into the organisms can occur, and that the complex between dihydrostreptomycin and inhibition sites cannot dissociate to give active antibiotic which could re-enter the ‘pool’.


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