Comparative effects of 5-fluorouracil on strains of Bacillus megaterium.

Wachsman, J. T. (University of Illinois, Urbana), S. Kemp, and L. Hogg. Comparative effects of 5-fluorouracil on strains of Bacillus megaterium. J. Bacteriol. 87:1011-1018. 1964.-Growth of Bacillus megaterium strain KM is severely inhibited by 5-fluorouracil (FU). Both thymidine and uridine are required to overcome this inhibition. The addition of uridine alone to a FU-inhibited culture permits good ribonucleic acid (RNA) and protein synthesis for the first 2 hr, but rather poor deoxyribonucleic acid synthesis. Uridine enhances the bactericidal effect of FU, promoting a decrease in the viable count of from 4 to 5 decades in 5 hr. Death begins after a 1-hr lag and is accompanied by hydrolysis of RNA and cell lysis, commencing during the 2- to 5-hr interval. The combination of FU and uridine is not bactericidal, when a methionine auxotroph is deprived of its required amino acid. Substrains of KM, partially resistant to FU, were isolated. Strain T(2) requires only thymidine to overcome the inhibitory effects of FU, whereas strain FU/2 requires only uridine. With a uridine auxotroph of strain KM, FU partially replaces uridine by permitting a small, but reproducible, increase in the amount of protein.