Antibiotics Inhibit Protein Synthesis Research Articles

Protein synthesis and amnesia: Studies with emetine and pactamycin

Two antibiotic inhibitors of protein synthesis, emetine and pactamycin, have been tested for their effects on cerebral and peripheral protein synthesis and amnesia. Peripherally administered emetine but not pactamycin inhibited cerebral protein synthesis, although this inhibition was lower than that observed with cycloheximide or anisomycin. Pactamycin had a lesser effect on adrenal protein synthesis than emetine. This was reflected in the ability of emetine but not pactamycin to block ACTH-induced corticosteroidogenesis. Anisomycin and cycloheximide caused amnesia in a passive avoidance task, whereas pactamycin and emetine did not. These results are inconsistent with the amnesia being due to inhibition of protein synthesis in a peripheral organ. They are also inconsistent with the amnesia being due to the suppression of an adrenocortical response as previously suggested. No obvious correlation between amnesia and the mechanism of protein synthesis was observed. The most parsimonious explanation is that inhibition of cerebral protein synthesis is necessary for amnesia.

Ferredoxin biosynthesis in Euglena gracilis

Analysis of ferredoxin content in cultures of Euglena gracilis grown in the presence of selective antibiotic inhibitors of protein synthesis resulted in the following conclusions: 1. 1. Ferredoxin is synthesized from cytoplasmic (80s-type) ribosomes; cycloheximide, a potent inhibitor of 80s translation completely abolished the synthesis, while the inhibitors of 70s translation chloramphenicol and erythromycin were not effective. In addition, ferredoxin was detected in a streptomycin-bleached mutant that lacks the chloroplast structure and chloroplast DNA. 2. 2. Ferredoxin's transcript is presumably of nuclear origin; rifampicin, an inhibitor of chloroplast DNA-dependent RNA polymerase did not inhibit synthesis, while the streptomycin-bleached mutant continued to synthesize ferredoxin without chloroplast DNA.

Circadian rhythm of rna synthesis in rat liver: effect of protein synthesis-inhibiting antibiotics at different times of day

1. 1. The content of free nucleotides and nucleosides, determined by u.v. measurement, did not change significantly during 24 hours. 2. 2. The antibiotics cycloheximide, pactamycin, puromycin and fusidic acid inhibited [ 3H]leucine incorporation into rat liver proteins by about 90%: in the case of cycloheximide and pactamycin the effect continued at least over 3 or 4 hours, whereas even high doses of puromycin and fusidic acid were effective not longer than 90–150 minutes. 3. 3. When protein synthesis was inhibited by these antibiotics, [ 3H]uridine incorporation into three RNA fractions at 0700 and 1100 hours was altered: at 0700 hours, the labeling of the 65° C fraction was increased in all cases. At 1100 hours a relative decrease in the labeling of the 65° C fraction and a relative increase in the 4° C fraction could be observed. Puromycin had no effect at that time of day. 4. 4. Two hours after an injection of cycloheximide at 0700 hours the content of RNA in the nucleus increased, but remained at the normal level at 1500 hours. In both cases a pronounced increase followed by a decrease of the nuclear RNA content occurred within the first 60 minutes. 5. 5. The results support the assumption that protein-associated transport processes or permeabilities are involved in the circadian pattern of RNA labeling.

Einfluß von Inhibitoren der Protein‐ und Nucleinsäuresynthese auf die Gestalt des Nucleoids von Escherichia coli

AbstractThe influence of drugs on the shape and the size of nuclear bodies of Escherichia coli has been studied by electronmicroscopy and sedimentation experiments. Antibiotics inhibiting protein synthesis but not RNA synthesis decrease the size of the nuclear body. Inhibition of RNA synthesis brings about a disintegration of the compact structure of the nucleoid. From electronmicrographs it can be seen that most drugs cause a condensation of the nucleoplasm into one single coherent region. Inhibition of DNA synthesis does not have much influence on the shape of the nuclear body. It is concluded that mainly the transcription process affects the form of the nuclear body.

The effects of protein synthesis-inhibiting antibiotics on the puffing pattern of Drosophila salivary gland chromosomes in vitro

Incubation of salivary glands of Drosophila melanogaster larvae with protein synthesis-inhibiting antibiotics for 3–4 hr in vitro resulted in specific puff induction. From the puffs tested, cycloheximide (100 μg/ml) induced 63E, 47B and 50CD, pactamycin (100 μg/ml) 63E only. Puromycin (100 μg/ml) and fusidic acid (100 μg/ml) on the other hand induced the heat- and 2,4-dinitrophenol-sensitive group of puffs (Ashburner, 1970) when applied to glands of a certain developmental stage (∼117 hr). Puffs 63BC, 87A, 87B, and 93D were measured; the increase in size was, as in the other group, statistically significant. Combined treatment with equal doses of cycloheximide and puromycin lead to cycloheximide-specific puffing pattern only; the same was true for lower doses of cycloheximide (20 μg/ml). 1 μg/ml cycloheximide did not induce any of the puff groups but prevented inductions by puromycin. The kinetics of the puff induction is specific for the different puffs measured. The effect of puromycin could be prevented by adding α-amanitin (1 μg/ml) or by ouabain (10 −4 M), not, however, by adding ATP (10 −3 M). The results may indicate that puffs are regulated via protein repressors and/or activators, the action of which is influenced by energy dependent transport processes.

Morphokinetic reaction of Streptococcus faecalis (ATCC 9790) cells to the specific inhibition of macromolecular synthesis: nucleoid condensation on the inhibition of protein synthesis.

In glutaraldehyde-prefixed exponential-phase cells of Streptococcus faecalis the nucleoid is "frozen" in a dispersed configuration. Exposure of exponential-phase cells to threonine starvation or to antibiotics inhibiting protein synthesis resulted in progressive condensation of nucleoid fibrils producing an expanding central nucleoid zone or pool. The condensation of the nucleoid was observed to occur at a rate directly proportional to the rate of inhibition of protein synthesis. However, the extent of nucleoid condensation depended on continuing deoxyribonucleic acid synthesis. Significantly less nucleoid condensation occurred when cells were inhibited in deoxyribonucleic acid and protein synthesis than when cells were inhibited in protein synthesis alone. These results suggest a model in which, during nucleoid replication, the chromosome fibrils are normally maintained in a dispersed state by the active agents of transcription-translation, such as ribonucleic acid polymerase molecules and ribosomes.

Studies directed towards the total syntheses of the nucleoside antibiotics, gougerotin and blasticidin S.

Abstract

Studies on the formation of transfer ribonucleic acid-ribosome complexes. XI. Antibiotic effects on phenylalanyl-oligonucleotide binding to ribosomes.

The effect of antibiotics on the binding of phenylalanyl-oligonucleotide to ribosomes has been examined. The results show that many classes of antibiotics can interfere with binding of the aminoacyl-oligonucleotide terminus of tRNA to ribosomes: chloramphenicol, sparsomycin, D-WIN-5094, vernamycin A, PA114A, streptogramin, amicetin, gougerotin, tylosin, and spiramycin III. The results are consistent with the hypothesis that these antibiotics inhibit protein synthesis by interfering with the binding of the aminoacyl-end of aminoacyl-tRNA to ribosomes.

Subunit localization studies of antibiotic inhibitors of protein synthesis

Subunit localization studies of antibiotic inhibitors of protein synthesis

Association of fusidic acid sensitivity with G factor in a protein-synthesizing system

It was observed that fusidic acid and related steroidal antibiotics inhibit protein synthesis in the in vivo and in vitro bacterial systems ( Yamaki, 1965; Harvey et al., 1966; Tanaka et al., 1967). In an E. coli system, they inhibit ribosome-dependent GTPase reaction with G factor of transfer enzymes, and the grade of inhibition is parallel to that of polypeptide synthesis. It was further suggested by the experiments, using puromycin reaction, that the antibiotics inhibit translocation of peptidyl-tRNA on the ribosomes ( Tanaka et al., 1968). Fusidic acid inhibits GTPase activity, observed in combination of the ribosomes and G factor. The localization of fusidic acid sensitivity was further studied with respect to the ribosomes and G factor of drug-sensitive E. coli cells and those of resistant cells. The results are presented in this communication. It was demonstrated that the fusidic acid sensitivity is associated with G factor, but not with the ribosomes.

Studies on the treatment of molluscan schistosomiasis mansoni with antibiotics, non-antibiotic metabolic inhibitors, molluscicides and anti-schistosomal agents

50% of 16 antibiotics, non-antibiotic metabolic inhibitors, molluscicides and antischistosomal agents suppressed molluscan schistosomiasis mansoni. In addition to chloramphenicol which had previously been shown to do so, 3 other antibiotic inhibitors of protein synthesis also suppressed the disease (puromycin, erythromycin and streptomycin) as did both non-antibiotic metabolic inhibitors (6 mercaptopurine and methotrexate) and all 3 antischistosomal agents (antimony potassium tartrate, stibophen and lucanthone hydrochloride). Methotrexate was the first drug found to eradicate the infection rather than merely suppress it, and lucanthone hydrochloride is the most potent drug thus far discovered. In addition to suppression of the disease at 0·4 ppm, it completely prevents snail growth and egg laying at a concentration of 0·3 ppm.