Erythromycin, lincosamides, peptidyl-tRNA dissociation, and ribosome editing.
Inaccurate protein synthesis produces unstable beta-galactosidase, whose activity is rapidly lost at high temperature. Erythromycin, lincomycin, clindamycin, and celesticetin were shown to counteract the error-inducing effects of streptomycin on beta-galactosidase synthesized in the antibiotic-hypersensitive Escherichia coli strain DB-11 Met-. Newly synthesized beta-galactosidase was more easily inactivated by high temperatures when synthesized by bacteria partially starved for arginine, threonine, or methionine. Simultaneous treatment with erythromycin or lincomycin yielded beta-galactosidase that was inactivated by high temperatures less easily than during starvation alone, an effect attributed to stimulation of ribosome editing. When synthesized in the presence of canavanine, beta-galactosidase was inactivated by high temperature more easily but this effect could not be reversed by erythromycin. The first arginine in beta-galactosidase occurs at residue 13, so the effect of erythromycin during arginine starvation is probably to stimulate dissociation of erroneous peptidyl-tRNAs of at least that length. Correction of errors induced by methionine starvation is probably due to stimulation of dissociation of erroneous peptidyl-tRNAs bearing peptides at least 92 residues in length. All the effects of erythromycin or the tested lincosamides on protein synthesis are probably the result of stimulating the dissociation from ribosomes of peptidyl-tRNAs that are erroneous or short.
Menninger
J R
JR
Department of Biological Sciences, University of Iowa, Iowa City 52242-1324.
Coleman
R A
RA
Tsai
L N
LN
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D002981:Clindamycin / Q000494:pharmacology; D003470:Culture Media; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006358:Hot Temperature; D008034:Lincomycin / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D009154:Mutation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013307:Streptomycin / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D012346:RNA, Transfer, Amino Acyl; C019037:tRNA, peptidyl-; D013912:Threonine; D002981:Clindamycin; D004917:Erythromycin; D001120:Arginine; D008715:Methionine; D008034:Lincomycin; D002265:Carboxylic Ester Hydrolases; D001616:beta-Galactosidase; D013307:Streptomycin