Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1969 Jan;97(1):230–236. doi: 10.1128/jb.97.1.230-236.1969

Mechanism of Action of Nalidixic Acid on Escherichia coli VI. Cell-free Studies

James V Boyle 1, Thomas M Cook 1, William A Goss 1
PMCID: PMC249584  PMID: 4884814

Abstract

The effects of nalidixic acid in vitro on deoxyribonucleic acid (DNA)- polymerase (deoxyribonucleosidetriphosphate: DNA deoxynucleotidyltransferase, EC 2.7.7.7), deoxyribonucleotide kinases (ATP: deoxymono- and diphosphate phosphotransferases), and deoxyribosyl transferase (nucleoside: purine deoxyribosyltransferase, EC 2.4.2.6) were examined employing partially purified and crude extracts of Escherichia coli ATCC 11229 and E. coli 15TAU. Nalidixic acid had no inhibitory effect on the DNA-polymerase of the wild-type strain E. coli ATCC 11229 at concentrations of 1.4 × 10−3 to 2.8 × 10−3m. No inhibition of deoxyribonucleotide kinase activity was observed at concentrations of nalidixic acid ranging from 2 × 10−3 to 8.6 × 10−3m. Nalidixic acid (0.43 × 10−4 to 0.43 × 10−3m) had no inhibitory effect on the deoxyribosyl transferase activity of crude extracts obtained from E. coli ATCC 11229 or E. coli 15TAU. Analytical CsCl density gradient centrifugation demonstrated that the DNA obtained after treatment of E. coli 15TAU with nalidixic acid was not cross-linked. These results suggest that the prevention of DNA synthesis in vivo by nalidixic acid is not attributable to inhibition of DNA polymerase, deoxyribonucleotide kinase, deoxyribosyl transferase, or to cross-linking of the DNA of treated cells.

Full text

PDF
230

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbour S. D. Effect of nalidixic acid on conjugational transfer and expression of episomal lac genes in Escherichia coli K12. J Mol Biol. 1967 Sep 14;28(2):373–376. doi: 10.1016/s0022-2836(67)80016-0. [DOI] [PubMed] [Google Scholar]
  3. Boyle J. V., Goss W. A., Cook T. M. Induction of excessive deoxyribonucleic acid synthesis in Escherichia coli by nalidixic acid. J Bacteriol. 1967 Nov;94(5):1664–1671. doi: 10.1128/jb.94.5.1664-1671.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Budman D. R., Pardee A. B. Thymidine and thymine incorporation into deoxyribonucleic acid: inhibition and repression by uridine of thymidine phosphorylase of Escherichia coli. J Bacteriol. 1967 Nov;94(5):1546–1550. doi: 10.1128/jb.94.5.1546-1550.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cook T. M., Brown K. G., Boyle J. V., Goss W. A. Bactericidal action of nalidixic acid on Bacillus subtilis. J Bacteriol. 1966 Nov;92(5):1510–1514. doi: 10.1128/jb.92.5.1510-1514.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cook T. M., Goss W. A., Deitz W. H. Mechanism of Action of Nalidixic Acid on Escherichia coli V. Possible Mutagenic Effect. J Bacteriol. 1966 Feb;91(2):780–783. doi: 10.1128/jb.91.2.780-783.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deitz W. H., Cook T. M., Goss W. A. Mechanism of action of nalidixic acid on Escherichia coli. 3. Conditions required for lethality. J Bacteriol. 1966 Feb;91(2):768–773. doi: 10.1128/jb.91.2.768-773.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elliott W. H. The effects of antimicrobial agents on deoxyribonucleic acid polymerase. Biochem J. 1963 Mar;86(3):562–567. doi: 10.1042/bj0860562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FALASCHI A., KORNBERG A. ANTIMETABOLITES AFFECTING PROTEIN OR NUCLEIC ACID SYNTHESIS. PHLEOMYCIN, AN INHIBITOR OF DNA POLYMERASE. Fed Proc. 1964 Sep-Oct;23:940–945. [PubMed] [Google Scholar]
  10. GOSS W. A., DEITZ W. H., COOK T. M. MECHANISM OF ACTION OF NALIDIXIC ACID ON ESCHERICHIA COLI. J Bacteriol. 1964 Oct;88:1112–1118. doi: 10.1128/jb.88.4.1112-1118.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GOSS W. A., DEITZ W. H., COOK T. M. MECHANISM OF ACTION OF NALIDIXIC ACID ON ESCHERICHIA COLI.II. INHIBITION OF DEOXYRIBONUCLEIC ACID SYNTHESIS. J Bacteriol. 1965 Apr;89:1068–1074. doi: 10.1128/jb.89.4.1068-1074.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. IYER V. N., SZYBALSKI W. A MOLECULAR MECHANISM OF MITOMYCIN ACTION: LINKING OF COMPLEMENTARY DNA STRANDS. Proc Natl Acad Sci U S A. 1963 Aug;50:355–362. doi: 10.1073/pnas.50.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Imada A., Igarasi S. Ribosyl and deoxyribosyl transfer by bacterial enzyme systems. J Bacteriol. 1967 Nov;94(5):1551–1559. doi: 10.1128/jb.94.5.1551-1559.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KORNBERG A. Biologic synthesis of deoxyribonucleic acid. Science. 1960 May 20;131(3412):1503–1508. doi: 10.1126/science.131.3412.1503. [DOI] [PubMed] [Google Scholar]
  15. Karlström O., Larsson A. Significance of ribonucleotide reduction in the biosynthesis of deoxyribonucleotides in Escherichia coli. Eur J Biochem. 1967 Dec;3(2):164–170. doi: 10.1111/j.1432-1033.1967.tb19512.x. [DOI] [PubMed] [Google Scholar]
  16. LEHMAN I. R., BESSMAN M. J., SIMMS E. S., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. I. Preparation of substrates and partial purification of an enzyme from Escherichia coli. J Biol Chem. 1958 Jul;233(1):163–170. [PubMed] [Google Scholar]
  17. LESHER G. Y., FROELICH E. J., GRUETT M. D., BAILEY J. H., BRUNDAGE R. P. 1,8-NAPHTHYRIDINE DERIVATIVES. A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS. J Med Pharm Chem. 1962 Sep;91:1063–1065. doi: 10.1021/jm01240a021. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Lyman H. Specific inhibition of chloroplast replication in Euglena gracilis by nalidixic acid. J Cell Biol. 1967 Dec;35(3):726–730. doi: 10.1083/jcb.35.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Okazaki R., Okazaki T., Sakabe K., Sugimoto K., Sugino A. Mechanism of DNA chain growth. I. Possible discontinuity and unusual secondary structure of newly synthesized chains. Proc Natl Acad Sci U S A. 1968 Feb;59(2):598–605. doi: 10.1073/pnas.59.2.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reichard P. 4th FEBS Meeting's Plenary Lecture. The biosynthesis of deoxyribonucleotides. Eur J Biochem. 1968 Jan;3(3):259–266. doi: 10.1111/j.1432-1033.1968.tb19525.x. [DOI] [PubMed] [Google Scholar]
  22. SCHILDKRAUT C. L., MARMUR J., DOTY P. Determination of the base composition of deoxyribonucleic acid from its buoyant density in CsCl. J Mol Biol. 1962 Jun;4:430–443. doi: 10.1016/s0022-2836(62)80100-4. [DOI] [PubMed] [Google Scholar]
  23. SZYBALSKI W., IYER V. N. CROSSLINKING OF DNA BY ENZYMATICALLY OR CHEMICALLY ACTIVATED MITOMYCINS AND PORFIROMYCINS, BIFUNCTIONALLY "ALKYLATING" ANTIBIOTICS. Fed Proc. 1964 Sep-Oct;23:946–957. [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES