The selective inhibition of microbial RNA synthesis by salicylate

Abstract

Salicylic acid inhibited growth when added to logarithmic cultures of Bacillus cereus and Escherichia coli incubating at pH 6. At 0.25 and 1 mM salicylate, the generation time was increased by about 25 and 100 per cent respectively. The effect was reversible and could not be overcome by the addition of selected vitamins or metals. Growth inhibition varied inversely with pH, and was related to the concentration of undissociated acid. Cultures grown in the presence or absence of 1 mM salicylate, when compared after similar increases in bacterial turbidity, had identical cell number, and the formation of protein, cell wall and DNA were unchanged. RNA synthesis, on the other hand, was specifically depressed. This effect was associated with all species of RNA examined, and again was quantitatively related to the concentration of undissociated salicylic acid in the growth medium. The effect on RNA synthesis appeared to be unrelated to the known ability of salicylate to affect oxidation and to uncouple oxidative phosphorylation, since the selective effect on RNA synthesis could also be demonstrated for E. coli growing anaerobically in the presence of salicylate. RNA polymerase, though sensitive to higher concentrations of salicylate, was not inhibited by the salicylate concentrations effective on growing cells. Cellular ATP levels were not decreased by growth in the presence of salicylate. Although the mechanism of the effect on RNA is still unclear, several structurally related compounds, such as benzoate, anthranilate and acetylsalicylate, appeared also to selectively inhibit RNA synthesis though at higher concentrations. The possible relationship of these drug effects to a “shift-down” response is discussed.