Abstract
Serine hydroxamate, which inhibits the charging of seryl-transfer ribonucleic acid, reduced the synthesis of phospholipid and nucleic acids in Escherichia coli. This effect was analogous to depriving amino acid auxotrophs of their nutritional requirement and appears to be a manifestation of the stringent response shown by rel+ strains of E. coli. Amino acid starvation (serine or methionine) alone or serine hydroxamate treatment alone results in 60 to 80% inhibition of lipid accumulation, 90% inhibition of ribonucleic acid accumulation, and an increase in guanosine tetraphosphate (ppGpp). These three effects were reversed by addition of chloramphenicol (CM). A combination of serine starvation and serine hydroxamate treatment resulted in inhibition of lipid and RNA accumulation as well as an increase in ppGpp, but the consequences of the double block were not reversed by CM. We conclude that a strong interrelationship exists among these processes and that CM acts to relax a stringent response by mechanisms other than interference with ppGpp formation. All species of phospholipid were affected by a stringent response evoked by amino acid starvation or addition of serine hydroxamate, but in all cases the synthesis of phosphatidylethanolamine was most severely inhibited. Serine hydroxamate was not incorporated into lipid but specifically caused phosphatidylserine accumulation. Serine starvation produced a dramatic alteration of the distribution of isotope incorporated into phospholipid, which resulted from the stringent response compounded with the limitation of a substrate for phosphatidylserine synthesis.
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Selected References
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- Ames G. F. Lipids of Salmonella typhimurium and Escherichia coli: structure and metabolism. J Bacteriol. 1968 Mar;95(3):833–843. doi: 10.1128/jb.95.3.833-843.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BALLOU C. E., VILKAS E., LEDERER E. Structural studies on the myo-inositol phospholipids of Mycobacterium tuberculosis (var. bovis, strain BCG). J Biol Chem. 1963 Jan;238:69–76. [PubMed] [Google Scholar]
- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Ballesta J. P., Schaechter M. Effect of shift-down and growth inhibition on phospholipid metabolism of Escherichia coli. J Bacteriol. 1971 Jul;107(1):251–258. doi: 10.1128/jb.107.1.251-258.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cashel M., Lazzarini R. A., Kalbacher B. An improved method for thin-layer chromatography of nucleotide mixtures containing 32P-labelled orthophosphate. J Chromatogr. 1969 Mar 11;40(1):103–109. doi: 10.1016/s0021-9673(01)96624-5. [DOI] [PubMed] [Google Scholar]
- Cronan J. E., Jr A new method for selection of Escherichia coli mutants defective in membrane lipid synthesis. Nat New Biol. 1972 Nov 1;240(96):21–22. doi: 10.1038/newbio240021a0. [DOI] [PubMed] [Google Scholar]
- Cronan J. E., Vagelos P. R. Metabolism and function of the membrane phospholipids of Escherichia coli. Biochim Biophys Acta. 1972 Feb 14;265(1):25–60. doi: 10.1016/0304-4157(72)90018-4. [DOI] [PubMed] [Google Scholar]
- EIDLIC L., NEIDHARDT F. C. PROTEIN AND NUCLEIC ACID SYNTHESIS IN TWO MUTANTS OF ESCHERICHIA COLI WITH TEMPERATURE-SENSITIVE AMINOACYL RIBONUCLEIC ACID SYNTHETASES. J Bacteriol. 1965 Mar;89:706–711. doi: 10.1128/jb.89.3.706-711.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furrow M. H., Pizer L. I. Phospholipid synthesis in Escherichia coli infected with T4 bacteriophages. J Virol. 1968 Jun;2(6):594–605. doi: 10.1128/jvi.2.6.594-605.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golden N. G., Powell G. L. Stringent and relaxed control of phospholipid metabolism in Escherichia coli. J Biol Chem. 1972 Oct 25;247(20):6651–6658. [PubMed] [Google Scholar]
- Kaplan S. Chloramphenicol and the stimulation of ribonucleic acid synthesis in Escherichia coli. J Bacteriol. 1969 May;98(2):587–592. doi: 10.1128/jb.98.2.587-592.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan S. Correlation between the rate of ribonucleic acid synthesis and the level of valyl transfer ribonucleic acid in mutants of Escherichia coli. J Bacteriol. 1969 May;98(2):579–586. doi: 10.1128/jb.98.2.579-586.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazzarini R. A., Cashel M., Gallant J. On the regulation of guanosine tetraphosphate levels in stringent and relaxed strains of Escherichia coli. J Biol Chem. 1971 Jul 25;246(14):4381–4385. [PubMed] [Google Scholar]
- Smith H. S., Pizer L. I. Abortive infection of Escherichia coli strain W by T2 bacteriophage. J Mol Biol. 1968 Oct 14;37(1):131–149. doi: 10.1016/0022-2836(68)90078-8. [DOI] [PubMed] [Google Scholar]
- Sokawa J., Sokawa Y., Kaziro Y. Stringent control in Escherichia coli. Nat New Biol. 1972 Dec 20;240(103):242–245. doi: 10.1038/newbio240242a0. [DOI] [PubMed] [Google Scholar]
- Sokawa Y., Nakao E., Kaziro Y. On the nature of the control by RC gene in e. coli: amino acid-dependent control of lipid synthesis. Biochem Biophys Res Commun. 1968 Oct 10;33(1):108–112. doi: 10.1016/0006-291x(68)90263-5. [DOI] [PubMed] [Google Scholar]
- Tosa T., Pizer L. I. Biochemical bases for the antimetabolite action of L-serine hydroxamate. J Bacteriol. 1971 Jun;106(3):972–982. doi: 10.1128/jb.106.3.972-982.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tosa T., Pizer L. I. Effect of serine hydroxamate on the growth of Escherichia coli. J Bacteriol. 1971 Jun;106(3):966–971. doi: 10.1128/jb.106.3.966-971.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]