The Origin of Bacterial Resistance to Proflavine: 4. Cycles of Resistance in Escherichia coli and their Bearing on Variations in Resistance in Cultures

Abstract

Small amounts of proflavine were added at intervals of 30 min to growing cultures of Escherichia coli. Additions during the logarithmic phase gave an increase of resistance of 2-or 3-fold in a high proportion of organisms. Additions in the lag or late logarithmic phase gave no such increase, although the resistance of the organisms themselves was higher in these phases. Whether organisms were able to grow in the presence of proflavine, therefore, depended not only on their resistance but on the conditions of the culture medium. The increase in proflavine resistance, which occurred when drug was added to growing cultures, was not accompanied by increase of cross-resistance to other drugs. The resistance was lost after growth in the absence of drug. For these reasons, the increase is held to be a phenotypic adaptation. There was also an increase in the number of organisms with a high resistance, of the same order as that of mutants. These organisms showed cross resistance with other drugs. Partial synchronization of division was achieved by the temporary cooling of cultures. These synchronized cultures showed cycles of division of about 30 min. They also showed cycles of resistance of about 20 min. Evidence is presented for the view that the organisms undergo cycles of varying adaptability to proflavine resistance. It is suggested that this variation in adaptability can explain the range of resistance found in an ordinary sensitive culture. It can also explain the effect of proflavine additions in raising the resistance of a high proportion or organisms in a growing culture.