SOME EFFECTS OF CHLORAMPHENICOL ON BIOSYNTHESIS IN BACILLUS CEREUS

¹ Department of Pharmacology, The George Washington University School of Medicine, Washington, D. C.

The presence of 10 µg of chloramphenicol per ml in an exponentially growing culture of Bacillus cereus resulted in partial inhibition of growth. The uptake of methionine-S³⁵ and other precursors which label protoplasmic protein exclusively was strongly depressed, while that of radiophosphate and cell wall components such as diaminopimelic acid continued, but at a rate reduced from that of control cells. It was concluded that per cell, RNA, DNA and cell wall accumulated during inhibition of growth in the virtual absence of protein synthesis.

A redistribution of radioactivity from exogenous cystine-S³⁵ in drug-treated cells was observed, in that considerably more isotope was hot-acid-extractable and probably was associated with nucleic acids. Experiments with lysine-C¹⁴ did not behave similarly.

RNA synthesized during growth inhibition of B. cereus showed only very slight instability after removal of the drug. Chloramphenicol impeded the formation of nucleic acid adenylic acid from exogenous adenine or guanine while the corresponding conversions to RNA guanylic acid were relatively unaffected. The utilization of uracil or uridine for RNA pyrimidines was profoundly depressed, while orotic acid and phosphate continued to be incorporated into RNA. Thus the drug affected specifically the incorporation of preformed bases into nucleic acids which, however, could still be synthesized de novo. The possible implication of this result to bone marrow toxicity has been discussed. A drug effect on uracil cofactors was also described.

Lower concentrations of chloramphenicol produced a similar effect on the growth rate but recovery took place sooner. Amino acids were again incorporated, apparently after the drug had been metabolized.

The striking similarities between the actions and biochemical effects of chloramphenicol and 8-azaguanine in B. cereus have been described.