Streptomycin-induced synthesis of abnormal protein in an Escherichia coli mutant.
To determine directly the effects of streptomycin on translational fidelity in intact cells, we studied the synthesis of beta-galactosidase and of the coat protein of bacteriophage R17 in an Escherichia coli mutant in which the bactericidal effects of streptomycin are delayed. After the addition of streptomycin to exponentially growing mutant cells, protein synthesis continues at an undiminished rate for approximately an hour; however, as measured by enzyme assays, little functional protein is produced. Serological assays designed to detect beta-galactosidase and bacteriophage R17 coat protein show that substantial amounts of the protein synthesized can react with antisera prepared against active beta-galactosidase and phage R17, indicating the aberrance of the protein produced in the presence of the antibiotic. The polypeptides synthesized in the presence of streptomycin are degraded in the cell to a much greater extent than protein synthesized in the absence of the antibiotic. The proteolytic attack on this protein is not affected by inhibitors of serine proteases, suggesting that enzymes other than those involved in "normal turnover" of cellular protein are responsible. In this strain, certain of the multiple effects of streptomycin are separated in time and the production of abnormal protein (enzymatically inactive and susceptible to proteolytic attack) could be studied in the absence of the lethal effect of the drug.
D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003429:Cross Reactions; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D005696:Galactosidases / Q000096:biosynthesis*; D009154:Mutation; D010452:Peptide Biosynthesis; D010649:Phenylalanine / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011489:Protein Denaturation / Q000187:drug effects; D013307:Streptomycin / Q000494:pharmacology*; D014105:Tosyl Compounds / Q000494:pharmacology; D014316:Tritium
D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D014105:Tosyl Compounds; D014316:Tritium; D010649:Phenylalanine; D001120:Arginine; D005696:Galactosidases; D013307:Streptomycin