Apparent Suppression of Mutation Rates in Bacteria by Spermine

Abstract

ONE of the chief obstacles to chemotherapy with antibiotics has been the frequent emergence of drug-tolerant bacteria. The availability of means to prevent or suppress the development of resistant cultures could have immense medical import as well as providing a valuable tool for the study of mutagenesis. Sevag and collaborators^1–3 reported that when polyamines were included in the culture medium of various micro-organisms, the outgrowth of drug-resistant populations in the presence of low concentrations of antibiotics was significantly delayed. They interpreted these observations as suggesting an antimutagenic role for the polyamines and further proposed that the site for this antimutagenic action is the DNA of the sensitive cells. Because of the theoretical implications of these observations it was of interest to establish in a more rigorous manner whether polyamines are antimutagens or whether the effects described by Sevag and co-workers could be explained in some other manner. This communication presents evidence that the inclusion of spermine in bacterial culture media resulted in a significant decrease in the random mutation rate of Escherichia coli and Staphylococcus aureus. The mutational events which were investigated were the one-step development of resistance to streptomycin and the back mutation to autotrophic growth by a tryptophan-requiring mutant. Spermine caused even more striking antimutagenic effects when mutations were induced by the inclusion of caffeine in the culture medium⁴ or by ultra-violet light. Future papers will seek to demonstrate that bacterial DNA could be the site of action of this compound⁵. A preliminary report on some of these experiments has already been given⁶.