Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Jul;39(7):1621–1623. doi: 10.1128/aac.39.7.1621

Salmonella typhimurium gyrA mutations associated with fluoroquinolone resistance.

F Reyna 1, M Huesca 1, V González 1, L Y Fuchs 1
PMCID: PMC162795  PMID: 7492118

Abstract

Spontaneous quinolone-resistant mutants obtained from Salmonella typhimurium Su694 were screened for mutations by direct DNA sequencing of an amplified PCR gyrA fragment. Substitutions Ser-83-->Phe (Ser83Phe), Ser83Tyr, Asp87Tyr, and Asp87Asn and double mutation Ala67Pro-Gly81Ser, which resulted in decreased sensitivities to ciprofloxacin, enoxacin, pefloxacin, norfloxacin, ofloxacin, and nalidixic acid, were found. The levels of resistance to quinolones for each mutant were determined.

Full Text

The Full Text of this article is available as a PDF (178.0 KB).

Selected References

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

  1. Brockbank S. M., Barth P. T. Cloning, sequencing, and expression of the DNA gyrase genes from Staphylococcus aureus. J Bacteriol. 1993 Jun;175(11):3269–3277. doi: 10.1128/jb.175.11.3269-3277.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bustos-Martinez J. A., Gomez-Eichelmann M. C. Frequency of IS1-mediated molecular events in different members of the family Enterobacteriaceae. J Bacteriol. 1987 Nov;169(11):4946–4949. doi: 10.1128/jb.169.11.4946-4949.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cambau E., Sougakoff W., Jarlier V. Amplification and nucleotide sequence of the quinolone resistance-determining region in the gyrA gene of mycobacteria. FEMS Microbiol Lett. 1994 Feb 1;116(1):49–54. doi: 10.1111/j.1574-6968.1994.tb06674.x. [DOI] [PubMed] [Google Scholar]
  4. Colman S. D., Hu P. C., Bott K. F. Mycoplasma pneumoniae DNA gyrase genes. Mol Microbiol. 1990 Jul;4(7):1129–1134. doi: 10.1111/j.1365-2958.1990.tb00687.x. [DOI] [PubMed] [Google Scholar]
  5. Dimri G. P., Das H. K. Cloning and sequence analysis of gyrA gene of Klebsiella pneumoniae. Nucleic Acids Res. 1990 Jan 11;18(1):151–156. doi: 10.1093/nar/18.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drlica K. Control of bacterial DNA supercoiling. Mol Microbiol. 1992 Feb;6(4):425–433. doi: 10.1111/j.1365-2958.1992.tb01486.x. [DOI] [PubMed] [Google Scholar]
  7. Drlica K., Coughlin S. Inhibitors of DNA gyrase. Pharmacol Ther. 1989;44(1):107–121. doi: 10.1016/0163-7258(89)90093-4. [DOI] [PubMed] [Google Scholar]
  8. Fuchs L. Y., González V. M., Bahena M., Reyna F., Chihu L., Ovando C. In-vitro selection of fluoroquinolone resistance in Salmonella typhimurium. J Antimicrob Chemother. 1993 Jul;32(1):171–172. doi: 10.1093/jac/32.1.171. [DOI] [PubMed] [Google Scholar]
  9. Gellert M., Mizuuchi K., O'Dea M. H., Itoh T., Tomizawa J. I. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4772–4776. doi: 10.1073/pnas.74.11.4772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gellert M., Mizuuchi K., O'Dea M. H., Nash H. A. DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3872–3876. doi: 10.1073/pnas.73.11.3872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gellert M., O'Dea M. H., Itoh T., Tomizawa J. Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4474–4478. doi: 10.1073/pnas.73.12.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goswitz J. J., Willard K. E., Fasching C. E., Peterson L. R. Detection of gyrA gene mutations associated with ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus: analysis by polymerase chain reaction and automated direct DNA sequencing. Antimicrob Agents Chemother. 1992 May;36(5):1166–1169. doi: 10.1128/aac.36.5.1166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hallett P., Maxwell A. Novel quinolone resistance mutations of the Escherichia coli DNA gyrase A protein: enzymatic analysis of the mutant proteins. Antimicrob Agents Chemother. 1991 Feb;35(2):335–340. doi: 10.1128/aac.35.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heisig P. High-level fluoroquinolone resistance in a Salmonella typhimurium isolate due to alterations in both gyrA and gyrB genes. J Antimicrob Chemother. 1993 Sep;32(3):367–377. doi: 10.1093/jac/32.3.367. [DOI] [PubMed] [Google Scholar]
  15. Heisig P., Tschorny R. Characterization of fluoroquinolone-resistant mutants of escherichia coli selected in vitro. Antimicrob Agents Chemother. 1994 Jun;38(6):1284–1291. doi: 10.1128/aac.38.6.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Higgins N. P., Peebles C. L., Sugino A., Cozzarelli N. R. Purification of subunits of Escherichia coli DNA gyrase and reconstitution of enzymatic activity. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1773–1777. doi: 10.1073/pnas.75.4.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holmes M. L., Dyall-Smith M. L. Mutations in DNA gyrase result in novobiocin resistance in halophilic archaebacteria. J Bacteriol. 1991 Jan;173(2):642–648. doi: 10.1128/jb.173.2.642-648.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hopewell R., Oram M., Briesewitz R., Fisher L. M. DNA cloning and organization of the Staphylococcus aureus gyrA and gyrB genes: close homology among gyrase proteins and implications for 4-quinolone action and resistance. J Bacteriol. 1990 Jun;172(6):3481–3484. doi: 10.1128/jb.172.6.3481-3484.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Horowitz D. S., Wang J. C. Mapping the active site tyrosine of Escherichia coli DNA gyrase. J Biol Chem. 1987 Apr 15;262(11):5339–5344. [PubMed] [Google Scholar]
  20. Ito H., Yoshida H., Bogaki-Shonai M., Niga T., Hattori H., Nakamura S. Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob Agents Chemother. 1994 Sep;38(9):2014–2023. doi: 10.1128/aac.38.9.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Korten V., Huang W. M., Murray B. E. Analysis by PCR and direct DNA sequencing of gyrA mutations associated with fluoroquinolone resistance in Enterococcus faecalis. Antimicrob Agents Chemother. 1994 Sep;38(9):2091–2094. doi: 10.1128/aac.38.9.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kureishi A., Diver J. M., Beckthold B., Schollaardt T., Bryan L. E. Cloning and nucleotide sequence of Pseudomonas aeruginosa DNA gyrase gyrA gene from strain PAO1 and quinolone-resistant clinical isolates. Antimicrob Agents Chemother. 1994 Sep;38(9):1944–1952. doi: 10.1128/aac.38.9.1944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Margerrison E. E., Hopewell R., Fisher L. M. Nucleotide sequence of the Staphylococcus aureus gyrB-gyrA locus encoding the DNA gyrase A and B proteins. J Bacteriol. 1992 Mar;174(5):1596–1603. doi: 10.1128/jb.174.5.1596-1603.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Maxwell A. The molecular basis of quinolone action. J Antimicrob Chemother. 1992 Oct;30(4):409–414. doi: 10.1093/jac/30.4.409. [DOI] [PubMed] [Google Scholar]
  25. Mizuuchi K., O'Dea M. H., Gellert M. DNA gyrase: subunit structure and ATPase activity of the purified enzyme. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5960–5963. doi: 10.1073/pnas.75.12.5960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moriya S., Ogasawara N., Yoshikawa H. Structure and function of the region of the replication origin of the Bacillus subtilis chromosome. III. Nucleotide sequence of some 10,000 base pairs in the origin region. Nucleic Acids Res. 1985 Apr 11;13(7):2251–2265. doi: 10.1093/nar/13.7.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oram M., Fisher L. M. 4-Quinolone resistance mutations in the DNA gyrase of Escherichia coli clinical isolates identified by using the polymerase chain reaction. Antimicrob Agents Chemother. 1991 Feb;35(2):387–389. doi: 10.1128/aac.35.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Palumbo M., Gatto B., Zagotto G., Palù G. On the mechanism of action of quinolone drugs. Trends Microbiol. 1993 Sep;1(6):232–235. doi: 10.1016/0966-842x(93)90138-h. [DOI] [PubMed] [Google Scholar]
  29. Rahman M., Mauff G., Levy J., Couturier M., Pulverer G., Glasdorff N., Butzler J. P. Detection of 4-quinolone resistance mutation in gyrA gene of Shigella dysenteriae type 1 by PCR. Antimicrob Agents Chemother. 1994 Oct;38(10):2488–2491. doi: 10.1128/aac.38.10.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Revel V., Cambau E., Jarlier V., Sougakoff W. Characterization of mutations in Mycobacterium smegmatis involved in resistance to fluoroquinolones. Antimicrob Agents Chemother. 1994 Sep;38(9):1991–1996. doi: 10.1128/aac.38.9.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sreedharan S., Oram M., Jensen B., Peterson L. R., Fisher L. M. DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli. J Bacteriol. 1990 Dec;172(12):7260–7262. doi: 10.1128/jb.172.12.7260-7262.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Swanberg S. L., Wang J. C. Cloning and sequencing of the Escherichia coli gyrA gene coding for the A subunit of DNA gyrase. J Mol Biol. 1987 Oct 20;197(4):729–736. doi: 10.1016/0022-2836(87)90479-7. [DOI] [PubMed] [Google Scholar]
  34. Takiff H. E., Salazar L., Guerrero C., Philipp W., Huang W. M., Kreiswirth B., Cole S. T., Jacobs W. R., Jr, Telenti A. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother. 1994 Apr;38(4):773–780. doi: 10.1128/aac.38.4.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vila J., Ruiz J., Marco F., Barcelo A., Goñi P., Giralt E., Jimenez de Anta T. Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs. Antimicrob Agents Chemother. 1994 Oct;38(10):2477–2479. doi: 10.1128/aac.38.10.2477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wang Y., Huang W. M., Taylor D. E. Cloning and nucleotide sequence of the Campylobacter jejuni gyrA gene and characterization of quinolone resistance mutations. Antimicrob Agents Chemother. 1993 Mar;37(3):457–463. doi: 10.1128/aac.37.3.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshida H., Bogaki M., Nakamura M., Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990 Jun;34(6):1271–1272. doi: 10.1128/aac.34.6.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES