Abstract
Escherichia coli K-12 carrying the R-factor R1 is resistant to ampicillin, chloramphenicol, and streptomycin. This resistance is due to R-factor-coded enzymes that metabolize the drugs. The effects of these enzymes on the survival of cell populations were studied in the presence of high concentrations of antibiotics. For all three antibiotics there were considerable inoculum effects. For ampicillin and chloramphenicol, the inoculum effect was due to detoxification of the medium, whereas streptomycin was not significantly metabolized. The survival of the population in the presence of streptomycin was due to the presence of resistant mutants. At high concentrations of ampicillin or chloramphenicol, the surviving cells were not mutants. Survival in the presence of ampicillin is presumably due to variations in resistance during the cell division cycle. The rate of acetylation of chloramphenicol decreased with time and was zero after 1 to 2 h. Treatment with high concentrations of chloramphenicol did not cause lysis of the cells but partially opened the outer membrane, causing excretion of beta-lactamase.