Studies on the Mechanism of Action of Nalidixic Acid

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1973 Oct 1

PMID 4208771

Citations 43

Authors

G J Bourguignon

M Levitt

R Sternglanz

Affiliations

Soon will be listed here.

Abstract

With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA. Also, no evidence has been found to support the hypothesis that nalidixic acid is permanently modified to a new, active compound by the bacterial cell. By using an in vitro DNA replication system developed by Bonhoeffer and colleagues, soluble extracts from nalidixic acid-sensitive cells have been shown to confer nalidixic acid sensitivity on the DNA synthesis of lysates from nalidixic acid-resistant cells. The activity in the extracts is only present in sensitive cells and is nondialyzable and heat sensitive. Finally, two known nalidixic acid-resistant mutants of Escherichia coli, mapping at nal A and nal B, respectively, have been tested to determine whether either of them is a transport mutant. It has been shown that nal B(r) is a transport mutant whereas nal A(r) is not.

Citing Articles

Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.

Warrier T, Romano K, Clatworthy A, Hung D Cell Chem Biol. 2022; 29(5):716-729.

PMID: 35523184 PMC: 9893512. DOI: 10.1016/j.chembiol.2022.04.006.

Diagnosis of quinolone-resistant Coxiella burnetii strains by PCR-RFLP.

Spyridaki I, Psaroulaki A, Aransay A, Scoulica E, Tselentis Y J Clin Lab Anal. 2000; 14(2):59-63.

PMID: 10683615 PMC: 6807793.

Mechanisms of quinolone resistance.

Wiedemann B, Heisig P Infection. 1994; 22 Suppl 2:S73-9.

PMID: 7927834 DOI: 10.1007/BF01793570.

Mechanisms of resistance to quinolones.

Cambau E, Gutmann L Drugs. 1993; 45 Suppl 3:15-23.

PMID: 7689446 DOI: 10.2165/00003495-199300453-00005.

In vitro and in vivo antibacterial activity of AB206, a new naphthyridine derivative.

Nagate T, Kurashige S, Mitsuhashi S Antimicrob Agents Chemother. 1980; 17(2):203-8.

PMID: 7387143 PMC: 283759. DOI: 10.1128/AAC.17.2.203.

References

Leive L . A NONSPECIFIC INCREASE IN PERMEABILITY IN ESCHERICHIA COLI PRODUCED BY EDTA. Proc Natl Acad Sci U S A. 1965; 53:745-50. PMC: 221061. DOI: 10.1073/pnas.53.4.745. View

Cummings D, Kusy A . Thymineless death in Escherichia coli: deoxyribonucleic acid replication and the immune state. J Bacteriol. 1970; 102(1):106-17. PMC: 284975. DOI: 10.1128/jb.102.1.106-117.1970. View

Schaller H, Otto B, Nusslein V, Huf J, Herrmann R, BONHOEFFER F . Deoxyribonucleic acid replication in vitro. J Mol Biol. 1972; 63(2):183-200. DOI: 10.1016/0022-2836(72)90369-5. View

Nusslein V, Otto B, BONHOEFFER F, Schaller H . Function of DNA polymerase 3 in DNA replication. Nat New Biol. 1971; 234(52):285-6. DOI: 10.1038/newbio234285a0. View

Hane M, Wood T . Escherichia coli K-12 mutants resistant to nalidixic acid: genetic mapping and dominance studies. J Bacteriol. 1969; 99(1):238-41. PMC: 249993. DOI: 10.1128/jb.99.1.238-241.1969. View

Winshell E, Rosenkranz H . Nalidixic Acid and the Metabolism of Escherichia coli. J Bacteriol. 1970; 104(3):1168-75. PMC: 248274. DOI: 10.1128/jb.104.3.1168-1175.1970. View

Cook T, Brown K, Boyle J, Goss W . Bactericidal action of nalidixic acid on Bacillus subtilis. J Bacteriol. 1966; 92(5):1510-4. PMC: 276451. DOI: 10.1128/jb.92.5.1510-1514.1966. View

Wickner R, Wright M, Wickner S, Hurwitz J . Conversion of phiX174 and fd single-stranded DNA to replicative forms in extracts of Escherichia coli. Proc Natl Acad Sci U S A. 1972; 69(11):3233-7. PMC: 389743. DOI: 10.1073/pnas.69.11.3233. View

Boyle J, Cook T, Goss W . Mechanism of action of nalidixic acid on Escherichia coli. Vi. Cell-free studies. J Bacteriol. 1969; 97(1):230-6. PMC: 249584. DOI: 10.1128/jb.97.1.230-236.1969. View

10.

Reich E, Goldberg I . Actinomycin and nucleic acid function. Prog Nucleic Acid Res Mol Biol. 1964; 3:183-234. DOI: 10.1016/s0079-6603(08)60742-4. View

11.

Wechsler J, Gross J . Escherichia coli mutants temperature-sensitive for DNA synthesis. Mol Gen Genet. 1971; 113(3):273-84. DOI: 10.1007/BF00339547. View

12.

Cowlishaw J, Ginoza W . Induction of lambda prophage by nalidixic acid. Virology. 1970; 41(2):244-55. DOI: 10.1016/0042-6822(70)90076-0. View

13.

Goss W, Deitz W, Cook T . MECHANISM OF ACTION OF NALIDIXIC ACID ON ESCHERICHIA COLI.II. INHIBITION OF DEOXYRIBONUCLEIC ACID SYNTHESIS. J Bacteriol. 1965; 89:1068-74. PMC: 277597. DOI: 10.1128/jb.89.4.1068-1074.1965. View

14.

GODSON G, SINSHEIMER R . Lysis of Escherichia coli with a neutral detergent. Biochim Biophys Acta. 1967; 149(2):476-88. DOI: 10.1016/0005-2787(67)90175-x. View

15.

NEUHARD J, Thomassen E . Turnover of the deoxyribonucleoside triphosphates in Escherichia coli 15 T during thymine starvation. Eur J Biochem. 1971; 20(1):36-43. DOI: 10.1111/j.1432-1033.1971.tb01359.x. View

16.

Pedrini A, Geroldi D, Siccardi A, Falaschi A . Studies on the mode of action of nalidixic acid. Eur J Biochem. 1972; 25(2):359-65. DOI: 10.1111/j.1432-1033.1972.tb01704.x. View

17.

Snyder F . RADIOASSAY OF THIN-LAYER CHROMATOGRAMS: A HIGH-RESOLUTION ZONAL SCRAPER FOR QUANTITATIVE C14 AND H3 SCANNING OF THIN-LAYER CHROMATOGRAMS. Anal Biochem. 1964; 9:183-96. DOI: 10.1016/0003-2697(64)90102-2. View

18.

Schekman R, Wickner W, Westergaard O, Brutlag D, Geider K, BERTSCH L . Initiation of DNA synthesis: synthesis of phiX174 replicative form requires RNA synthesis resistant to rifampicin. Proc Natl Acad Sci U S A. 1972; 69(9):2691-5. PMC: 427018. DOI: 10.1073/pnas.69.9.2691. View

19.

Gefter M, Hirota Y, Kornberg T, Wechsler J, Barnoux C . Analysis of DNA polymerases II and 3 in mutants of Escherichia coli thermosensitive for DNA synthesis. Proc Natl Acad Sci U S A. 1971; 68(12):3150-3. PMC: 389610. DOI: 10.1073/pnas.68.12.3150. View

20.

Fuchs J, Karlstrom H, Warner H, REICHARD P . Defective gene product in dnaF mutant of Escherichia coli. Nat New Biol. 1972; 238(81):69-71. DOI: 10.1038/newbio238069a0. View