present in the broth must be the same in both experiments. The nature of the preequilibrium process must be changed. Some investigators (40-42) studied permeation of oxytetracycline in sensitive and resistant cells at high antibiotic concentrations and found it depends upon an energy-requiring process. Franklin and Godfrey (11) verified a glucose-dependent uptake at low concentrations of tetracycline and chlortetracycline. The condition of the cells in these cultures is so different that it is hard to make meaningful comparisons. However, it seems clear that the ability to permeate the cells is an important factor in antibiotic acitivity, whether this process is an inactive or active diffusion.
SUMMARY
The kinetics of inhibition of cell division and protein and nucleic acid syntheses have been investigated for E. coli W cultures in the presence of a series of 18 tetracycline antibiotics. The rate constants for these parameters have been found to be linear functions of the antibiotic concentration. The proportionality constants have been found to be the same for all parameters and are reported as a measure of the activity of the analogs.
The time of onset of inhibition and the time of recovery from inhibition have been investigated; the order, protein synthesis occurring before either nucleic acid synthesis or cell division, has been observed. This order is interpreted as consistent with an inhibition of protein synthesis as the primary mode of action. The existence of a lag time for onset of inhibition of protein synthesis, its growth-rate independence, and its variation with broth pH are interpreted as due to the existence of a finite permeation time.