Erythromycin- and Chloramphenicol-Induced Ribosomal Assembly Defects Are Secondary Effects of Protein Synthesis Inhibition

Several protein synthesis inhibitors are known to inhibit ribosome assembly. This may be a consequence of direct binding of the antibiotic to ribosome precursor particles, or it could result indirectly from loss of coordination in the production of ribosomal components due to the inhibition of protein synthesis. Here we demonstrate that erythromycin and chloramphenicol, inhibitors of the large ribosomal subunit, affect the assembly of both the large and small subunits. Expression of a small erythromycin resistance peptide acting in cis on mature ribosomes relieves the erythromycin-mediated assembly defect for both subunits. Erythro-mycin treatment of bacteria expressing a mixture of erythromycin-sensitive and-resistant ribosomes produced comparable effects on subunit assembly. These results argue in favor of the view that erythromycin and chloramphenicol affect the assembly of the large ribosomal subunit indirectly. The ribosome is a target for many medically important an-tibiotics (42, 56, 63). These drugs bind to either the small or the large subunit and inhibit essential ribosome functions: decod-ing, peptidyl transfer, transit of the nascent peptide chain, or activation of ribosome-associated GTPases. In addition, anti-biotics cause many physiological changes; for example, the