Reevaluation of the mode of action of streptolydigin in Escherichia coli: induction of transcription termination in vivo.
Growth of the permeable strain AS19 of Escherichia 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 beta-galactosidase is inhibited relative to the synthesis of short, unstable polypeptides, which include the first 60 to 70 amino acids of beta-galactosidase. The expression of the following polycistronic transcription units is strongly biased against promoter-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. We suggest 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.
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010452:Peptide Biosynthesis; D012329:RNA, Bacterial / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012329:RNA, Bacterial