Abstract
In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on ribosomes and compared them to the effects of this antibiotic on growth and protein synthesis. We have shown that no changes in ribosome distribution are observed until growth inhibition by dihydrostreptomycin is almost complete. Thus, intracellular dihydrostreptomycin can inhibit growth and net protein synthesis without apparently affecting the ribosome cycle. Since it is known that the antibiotic combines with free 30S subunits, the question is how such combination can bring about the observed inhibition of protein synthesis and growth. We suggest that specific interaction of intracellular antibiotic with proteins of the 30S subunits allows repeated use of the ribosome cycle by such affected particles, but with selective misreading of certain amino acid codons as terminator codons, so that they produce incomplete polypeptide chains. The cumulative effect of such a mechanism would lead to eventual cessation of protein synthesis and growth.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Algranati I. D., Gonzalez N. S., Bade E. G. Physiological role of 70S ribosomes in bacteria. Proc Natl Acad Sci U S A. 1969 Feb;62(2):574–580. doi: 10.1073/pnas.62.2.574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Apirion D., Phillips S. L., Schlessinger D. Approaches to the genetics of Escherichia coli ribosomes. Cold Spring Harb Symp Quant Biol. 1969;34:117–128. doi: 10.1101/sqb.1969.034.01.018. [DOI] [PubMed] [Google Scholar]
- COX E. C., WHITE J. R., FLAKS J. G. STREPTOMYCIN ACTION AND THE RIBOSOME. Proc Natl Acad Sci U S A. 1964 Apr;51:703–709. doi: 10.1073/pnas.51.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang F. N., Flaks J. G. Topography of the Escherichia coli 30S ribosomal subunit and streptomycin binding. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1321–1328. doi: 10.1073/pnas.67.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIES J. E. STUDIES ON THE RIBOSOMES OF STREPTOMYCIN-SENSITIVE AND RESISTANT STRAINS OF ESCHERICHIA COLI. Proc Natl Acad Sci U S A. 1964 Apr;51:659–664. doi: 10.1073/pnas.51.4.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIES J., GILBERT W., GORINI L. STREPTOMYCIN, SUPPRESSION, AND THE CODE. Proc Natl Acad Sci U S A. 1964 May;51:883–890. doi: 10.1073/pnas.51.5.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DUBIN D. T., HANCOCK R., DAVIS B. D. THE SEQUENCE OF SOME EFFECTS OF STREPTOMYCIN IN ESCHERICHIA COLI. Biochim Biophys Acta. 1963 Aug 13;74:476–489. doi: 10.1016/0006-3002(63)91390-8. [DOI] [PubMed] [Google Scholar]
- DUBIN D. T. SOME EFFECT OF STREPTOMYCIN ON RNA METABOLISM IN ESCHERICHIA COLI. J Mol Biol. 1964 May;8:749–767. doi: 10.1016/s0022-2836(64)80122-4. [DOI] [PubMed] [Google Scholar]
- Davies J. Streptomycin and the genetic code. Cold Spring Harb Symp Quant Biol. 1966;31:665–670. doi: 10.1101/sqb.1966.031.01.085. [DOI] [PubMed] [Google Scholar]
- Davis B. D. Role of subunits in the ribosome cycle. Nature. 1971 May 21;231(5299):153–157. doi: 10.1038/231153a0. [DOI] [PubMed] [Google Scholar]
- ERDOS T., ULLMANN A. Effect of streptomycin on the incorporation of amino-acids labelled with carbon-14 into ribonucleic acid and protein in a cell-free system of a Mycobacterium. Nature. 1959 Feb 28;183(4661):618–619. doi: 10.1038/183618a0. [DOI] [PubMed] [Google Scholar]
- Eisenstadt J. M., Brawerman G. The role of the native subribosomal particles of Escherichia coli in polypeptide chain initiation. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1560–1565. doi: 10.1073/pnas.58.4.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FLAKS J. G., COX E. C., WHITE J. R. Inhibition of polypeptide synthesis by streptomycin. Biochem Biophys Res Commun. 1962 May 11;7:385–389. doi: 10.1016/0006-291x(62)90320-0. [DOI] [PubMed] [Google Scholar]
- FRIEDMAN S. M., WEINSTEIN I. B. LACK OF FIDELITY IN THE TRANSLATION OF SYNTHETIC POLYRIBONUCLEOTIDES. Proc Natl Acad Sci U S A. 1964 Oct;52:988–996. doi: 10.1073/pnas.52.4.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GORINI L., KATAJA E. PHENOTYPIC REPAIR BY STREPTOMYCIN OF DEFECTIVE GENOTYPES IN E. COLI. Proc Natl Acad Sci U S A. 1964 Mar;51:487–493. doi: 10.1073/pnas.51.3.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godson G. N., Sinsheimer R. L. Lysis of Escherichia coli with a neutral detergent. Biochim Biophys Acta. 1967 Dec 19;149(2):476–488. doi: 10.1016/0005-2787(67)90175-x. [DOI] [PubMed] [Google Scholar]
- Godson G. N., Sinsheimer R. L. Use of Brij lysis as a general method to prepare polyribosomes from Escherichia coli. Biochim Biophys Acta. 1967 Dec 19;149(2):489–495. doi: 10.1016/0005-2787(67)90176-1. [DOI] [PubMed] [Google Scholar]
- Gorini L. The contrasting role of strA and ram gene products in ribosomal functioning. Cold Spring Harb Symp Quant Biol. 1969;34:101–109. doi: 10.1101/sqb.1969.034.01.016. [DOI] [PubMed] [Google Scholar]
- HANCOCK R. Uptake of 14C-streptomycin by Bacillus megaterium. J Gen Microbiol. 1962 Jul;28:503–516. doi: 10.1099/00221287-28-3-503. [DOI] [PubMed] [Google Scholar]
- Hammond B. J., Kogut M., Lightbown J. W. Analogue computer studies of the growth characteristics of Escherichia coli following dihydrostreptomycin treatment. J Gen Microbiol. 1967 Aug;48(2):189–203. doi: 10.1099/00221287-48-2-189. [DOI] [PubMed] [Google Scholar]
- Hardy S. J., Turnock G. Silver plated ribosomes. Nat New Biol. 1971 Aug 4;232(31):152–153. doi: 10.1038/newbio232152a0. [DOI] [PubMed] [Google Scholar]
- Hardy S. J., Turnock G. Stabilization of 70S ribosomes by spermidine. Nat New Biol. 1971 Jan 6;229(1):17–19. doi: 10.1038/newbio229017a0. [DOI] [PubMed] [Google Scholar]
- KOGUT M., LIGHTBOWN J. W., ISAACSON P. EFFECTS OF DIHYDROSTREPTOMYCIN TREATMENT ON THE GROWTH OF ESCHERICHIA COLI AFTER REMOVAL OF EXTRACELLULAR ANTIBIOTIC. J Gen Microbiol. 1965 May;39:165–183. doi: 10.1099/00221287-39-2-165. [DOI] [PubMed] [Google Scholar]
- KOGUT M., LIGHTBROWN J. W., ISAACSON P. STREPTOMYCIN ACTION AND ANAEROBIOSIS. J Gen Microbiol. 1965 May;39:155–164. doi: 10.1099/00221287-39-2-155. [DOI] [PubMed] [Google Scholar]
- Kaempfer R. Dissociation of ribosomes on polypeptide chain termination and origin of single ribosomes. Nature. 1970 Nov 7;228(5271):534–537. doi: 10.1038/228534a0. [DOI] [PubMed] [Google Scholar]
- Kaempfer R., Meselson M. Studies of ribosomal subunit exchange. Cold Spring Harb Symp Quant Biol. 1969;34:209–220. doi: 10.1101/sqb.1969.034.01.027. [DOI] [PubMed] [Google Scholar]
- Kaji H., Kaji A. Specific binding of sRNA to ribosomes: effect of streptomycin. Proc Natl Acad Sci U S A. 1965 Jul;54(1):213–219. doi: 10.1073/pnas.54.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaji H., Tanaka Y. Binding of dihydrostreptomycin to ribosomal subunits. J Mol Biol. 1968 Mar 14;32(2):221–230. doi: 10.1016/0022-2836(68)90006-5. [DOI] [PubMed] [Google Scholar]
- Kogut M., Harris M. Effects of streptomycin in bacterial cultures growing at different rates; interaction with bacterial ribosomes in vivo. Eur J Biochem. 1969 May 1;9(1):42–49. doi: 10.1111/j.1432-1033.1969.tb00573.x. [DOI] [PubMed] [Google Scholar]
- Kogut M., Lightbown J. W., Isaacson P. The intracellular accumulation of 14-C-streptomycin by Escherichia coli strain B in relation to its growth-inhibitory effect. J Gen Microbiol. 1966 Mar;42(3):333–344. doi: 10.1099/00221287-42-3-333. [DOI] [PubMed] [Google Scholar]
- Kogut M., Maltby E. N., Prizant E. Effects of dihydrostreptomycin on bacterial ribosomes in vivo. Biochem J. 1970 Aug;119(1):121–123. doi: 10.1042/bj1190121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kogut M., Prizant E. The accumulation of "run-off" ribosomes during treatment of Escherichia coli with dihydrostreptomycin in vivo. J Gen Microbiol. 1972 May;70(3):567–570. doi: 10.1099/00221287-70-3-567. [DOI] [PubMed] [Google Scholar]
- Kogut Margot, Prizant Elaine. Effects of dihydrostreptomycin treatment in vivo on the ribosome cycle in Escherichia coli. FEBS Lett. 1970 Dec 23;12(1):17–20. doi: 10.1016/0014-5793(70)80583-x. [DOI] [PubMed] [Google Scholar]
- Lennette E. T., Apiriaon D. The level of Fmt-tRNA on ribosomes from streptomycin treated cells. Biochem Biophys Res Commun. 1970 Nov 9;41(3):804–811. doi: 10.1016/0006-291x(70)90084-7. [DOI] [PubMed] [Google Scholar]
- Luzzatto L., Apirion D., Schlessinger D. Mechanism of action of streptomycin in E. coli: interruption of the ribosome cycle at the initiation of protein synthesis. Proc Natl Acad Sci U S A. 1968 Jul;60(3):873–880. doi: 10.1073/pnas.60.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luzzatto L., Apirion D., Schlessinger D. Polyribosome depletion and blockage of the ribosome cycle by streptomycin in Escherichia coli. J Mol Biol. 1969 Jun 14;42(2):315–335. doi: 10.1016/0022-2836(69)90046-1. [DOI] [PubMed] [Google Scholar]
- Mangiarotti G., Schlessinger D. Polyribosome metabolism in Escherichia coli. I. Extraction of polyribosomes and ribosomal subunits from fragile, growing Escherichia coli. J Mol Biol. 1966 Sep;20(1):123–143. doi: 10.1016/0022-2836(66)90122-7. [DOI] [PubMed] [Google Scholar]
- Miall S. H., Kato T., Tamaoki T. A factor promoting dissociation of Escherichia coli ribosomes. Nature. 1970 Jun 13;226(5250):1050–1052. doi: 10.1038/2261050a0. [DOI] [PubMed] [Google Scholar]
- Modolell J., Davis B. D. Breakdown by streptomycin of initiation complexes formed on ribosomes of Escherichia coli. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1148–1155. doi: 10.1073/pnas.67.3.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Modolell J., Davis B. D. Mechanism of inhibition of ribosomes by streptomycin. Nature. 1969 Oct 25;224(5217):345–348. doi: 10.1038/224345a0. [DOI] [PubMed] [Google Scholar]
- Oxenburgh M. S., Snoswell A. M. Use of streptomycin in the separation of nucleic acids from protein in a bacterial extract. Nature. 1965 Sep 25;207(5004):1416–1417. doi: 10.1038/2071416a0. [DOI] [PubMed] [Google Scholar]
- PESTKA S., MARSHALL R., NIRENBERG M. RNA CODEWORDS AND PROTEIN SYNTHESIS. V. EFFECT OF STREPTOMYCIN ON THE FORMATION OF RIBOSOME-SRNA COMPLEXES. Proc Natl Acad Sci U S A. 1965 Mar;53:639–646. doi: 10.1073/pnas.53.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pestka S., Nirenberg M. Codeword recognition on 30 S ribosomes. Cold Spring Harb Symp Quant Biol. 1966;31:641–656. doi: 10.1101/sqb.1966.031.01.083. [DOI] [PubMed] [Google Scholar]
- Ron E. Z., Kohler R. E., Davis B. D. Magnesium ion dependence of free and polysomal ribosomes from Escherichia coli. J Mol Biol. 1968 Aug 28;36(1):83–89. doi: 10.1016/0022-2836(68)90221-0. [DOI] [PubMed] [Google Scholar]
- Ron E. Z., Kohler R. E., Davis B. D. Polysomes extracted from Escherichia coli by freeze-thaw-lysozyme lysis. Science. 1966 Sep 2;153(3740):1119–1120. doi: 10.1126/science.153.3740.1119. [DOI] [PubMed] [Google Scholar]
- SCHAECHTER M., MAALOE O., KJELDGAARD N. O. Dependency on medium and temperature of cell size and chemical composition during balanced grown of Salmonella typhimurium. J Gen Microbiol. 1958 Dec;19(3):592–606. doi: 10.1099/00221287-19-3-592. [DOI] [PubMed] [Google Scholar]
- Schwartz J. H. An effect of streptomycin on the biosynthesis of the coat protein of coliphage f2 by extract of E. coli. Proc Natl Acad Sci U S A. 1965 May;53(5):1133–1140. doi: 10.1073/pnas.53.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stern J. L., Barner H. D., Cohen S. S. The lethality of streptomycin and the stimulation of RNA synthesis in the absence of protein synthesis. J Mol Biol. 1966 May;17(1):188–217. doi: 10.1016/s0022-2836(66)80103-1. [DOI] [PubMed] [Google Scholar]
- Subramanian A. R., Davis B. D. Activity of initiation factor F3 in dissociating Escherichia coli ribosomes. Nature. 1970 Dec 26;228(5278):1273–1275. doi: 10.1038/2281273a0. [DOI] [PubMed] [Google Scholar]
- Subramanian A. R., Davis B. D., Beller R. J. The ribosome dissociation factor and the ribosome-polysome cycle. Cold Spring Harb Symp Quant Biol. 1969;34:223–230. doi: 10.1101/sqb.1969.034.01.028. [DOI] [PubMed] [Google Scholar]
- Subramanian A. R., Davis B. D. Rapid exchange of subunits between free ribosomes in extracts of Escherichia coli. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2453–2457. doi: 10.1073/pnas.68.10.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Subramanian A. R., Ron E. Z., Davis B. D. A factor required for ribosome dissociation in Escherichia coli. Proc Natl Acad Sci U S A. 1968 Oct;61(2):761–767. doi: 10.1073/pnas.61.2.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson J. A., Schubert J. Action of hydrogen peroxide on growth inhibition of Salmonella typhimurium. J Gen Microbiol. 1969 Jul;57(1):25–34. doi: 10.1099/00221287-57-1-25. [DOI] [PubMed] [Google Scholar]
- Weisblum B., Davies J. Antibiotic inhibitors of the bacterial ribosome. Bacteriol Rev. 1968 Dec;32(4 Pt 2):493–528. [PMC free article] [PubMed] [Google Scholar]
- Wolfe A. D., Hahn F. E. Stability of ribosomes from streptomycin-exposed Escherichia coli. Biochem Biophys Res Commun. 1968 Jun 28;31(6):945–949. doi: 10.1016/0006-291x(68)90544-5. [DOI] [PubMed] [Google Scholar]
