Reevaluation of the mode of action of streptolydigin in Escherichia coli: induction of transcription termination in vivo

Abstract

Growth of the permeable strain AS19 of E. coli B is more sensitive to the antibiotic streptolydigin than is in vitro ribonucleic acid (RNA) synthesis. The in vivo chain elongation rates of lacZ messenger RNA and ribosomal RNA are not affected at 1.5 x 10 -6 M, a concentration that reduces the growth rate threefold. The synthesis of large proteins is inhibited preferentially, and a considerable fraction of the polypeptides synthesized is unstable. The synthesis of complete β-galactosidase is inhibited relative to the synthesis of short, unstable polypeptides, which include the first 60 to 70 amino acids of β-galactosidase. The expression of the following polycistronic transcription units is strongly biased against promotor-distal genes: trp, deo, rpoBC, and rrn. The extent of polarity is proportional to the distance transcribed and to the streptolydigin concentration. Streptolydigin appears to destabilize active transcription complexes irreversibly irrespective of the type of transcript (messenger RNA, ribosomal RNA) and of transcription intensity. It is suggested that streptolydigin leads to premature termination of transcription, resulting in release of incomplete transcripts and thus, a decrease in overall messenger RNA concentration, which becomes limiting for protein synthesis, i.e., for growth.