Specific inhibition of ribosomal RNA synthesis in escherichia coli by tetracycline

Abstract

Five Hundred μg/ml tetracycline was found to inhibit the accumulation of RNA in Escherichia coli cells. RNA synthesis was not totally inhibited, however. On the contrary, by using DNA-RNA hybridization, it was found that 500 μg/ml tetracycline specifically inhibits ribosomal RNA (rRNA) synthesis but allows messenger RNA synthesis to continue. Also, tetracycline specifically inhibits initiation of ribosomal RNA synthesis as determined from rate studies. The inhibition of rRNA synthesis at 500 μg/ml tetracycline was not due to several trivial explanations, that is, stimulation of ppGpp synthesis, inhibition of nucleoside triphosphate synthesis, nor was it due to sequestering of magnesium ion necessary for RNA polymerase action. Also, 500 μg/ml tetracycline was not inhibitory to RNA synthesis in permeabilized cells capable of normal rates of rRNA synthesis, similar to data previously obtained using ppGpp. Thus, it is proposed that tetracycline stops rRNA synthesis by inhibiting a ribosomal specific transcription factor; this factor is lost or destroyed during cell permeabilization. It is further proposed that tetracycline acts in a manner analogous to the normal rRNA regulator molecule (very likely ppGpp) at the transcriptional level.