Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Jan;39(1):87–93. doi: 10.1128/aac.39.1.87

Frequency and mechanism of resistance to antibacterial action of ZM 240401, (6S)-6-fluoro-shikimic acid.

C D Ewart 1, D A Jude 1, J L Thain 1, W W Nichols 1
PMCID: PMC162490  PMID: 7695335

Abstract

Spontaneous resistance to (6S)-6-fluoro-shikimic acid arose in Escherichia coli and other enterobacteria at high frequencies, between 10(-5) and 10(-4). Two resistant variants of E. coli were tested for their susceptibilities to the diastereomeric compound, (6R)-6-fluoro-shikimate, and both of them had become resistant to this compound as well. (6S)-6-Fluoro-shikimate-resistant variants of E. coli generally failed to transport [14C]shikimate. In E. coli K-12, (6S)-6-fluoro-shikimate resistance cotransduced with his at the same frequency as shiA, a gene locus that governs shikimate transport phenotypes. We propose that the loss of susceptibility to (6S)-6-fluoro-shikimic acid in spontaneous resistant variants is due to the loss of activity of the transport system by which it enters the bacterial cytoplasm.

Full Text

The Full Text of this article is available as a PDF (248.0 KB).

Selected References

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

  1. Bachmann B. J. Linkage map of Escherichia coli K-12, edition 8. Microbiol Rev. 1990 Jun;54(2):130–197. doi: 10.1128/mr.54.2.130-197.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barth P. T., Datta N., Hedges R. W., Grinter N. J. Transposition of a deoxyribonucleic acid sequence encoding trimethoprim and streptomycin resistances from R483 to other replicons. J Bacteriol. 1976 Mar;125(3):800–810. doi: 10.1128/jb.125.3.800-810.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bentley R. The shikimate pathway--a metabolic tree with many branches. Crit Rev Biochem Mol Biol. 1990;25(5):307–384. doi: 10.3109/10409239009090615. [DOI] [PubMed] [Google Scholar]
  4. Brown K. D., Doy C. H. Transport and utilization of the biosynthetic intermediate shikimic acid in Escherichia coli. Biochim Biophys Acta. 1976 May 28;428(3):550–562. doi: 10.1016/0304-4165(76)90183-5. [DOI] [PubMed] [Google Scholar]
  5. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davies G. M., Barrett-Bee K. J., Jude D. A., Lehan M., Nichols W. W., Pinder P. E., Thain J. L., Watkins W. J., Wilson R. G. (6S)-6-fluoroshikimic acid, an antibacterial agent acting on the aromatic biosynthetic pathway. Antimicrob Agents Chemother. 1994 Feb;38(2):403–406. doi: 10.1128/aac.38.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dewick P. M. The biosynthesis of shikimate metabolites. Nat Prod Rep. 1993 Jun;10(3):233–263. doi: 10.1039/np9931000233. [DOI] [PubMed] [Google Scholar]
  8. Dougan G. 1993 Colworth Prize Lecture. The molecular basis for the virulence of bacterial pathogens: implications for oral vaccine development. Microbiology. 1994 Feb;140(Pt 2):215–224. doi: 10.1099/13500872-140-2-215. [DOI] [PubMed] [Google Scholar]
  9. Green J. M., Merkel W. K., Nichols B. P. Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J Bacteriol. 1992 Aug;174(16):5317–5323. doi: 10.1128/jb.174.16.5317-5323.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Green J. M., Nichols B. P. p-Aminobenzoate biosynthesis in Escherichia coli. Purification of aminodeoxychorismate lyase and cloning of pabC. J Biol Chem. 1991 Jul 15;266(20):12971–12975. [PubMed] [Google Scholar]
  11. HERSHEY A. D. An upper limit to the protein content of the germinal substance of bacteriophage T2. Virology. 1955 May;1(1):108–127. doi: 10.1016/0042-6822(55)90009-x. [DOI] [PubMed] [Google Scholar]
  12. King A., Shannon K., Eykyn S., Phillips I. Reduced sensitivity to beta-lactam antibiotics arising during ceftazidime treatment of Pseudomonas aeruginosa infections. J Antimicrob Chemother. 1983 Oct;12(4):363–370. doi: 10.1093/jac/12.4.363. [DOI] [PubMed] [Google Scholar]
  13. MONOD J., COHEN-BAZIRE G., COHN M. Sur la biosynthèse de la beta-galactosidase (lactase) chez Escherichia coli; la spécificité de l'induction. Biochim Biophys Acta. 1951 Nov;7(4):585–599. doi: 10.1016/0006-3002(51)90072-8. [DOI] [PubMed] [Google Scholar]
  14. Milatovic D., Braveny I. Development of resistance during antibiotic therapy. Eur J Clin Microbiol. 1987 Jun;6(3):234–244. doi: 10.1007/BF02017607. [DOI] [PubMed] [Google Scholar]
  15. Pittard J., Wallace B. J. Gene controlling the uptake of shikimic acid by Escherichia coli. J Bacteriol. 1966 Oct;92(4):1070–1075. doi: 10.1128/jb.92.4.1070-1075.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Quinn J. P., Dudek E. J., DiVincenzo C. A., Lucks D. A., Lerner S. A. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis. 1986 Aug;154(2):289–294. doi: 10.1093/infdis/154.2.289. [DOI] [PubMed] [Google Scholar]
  17. Taylor D., Holland K. T. Amino acid requirements for the growth and production of some exocellular products of Staphylococcus aureus. J Appl Bacteriol. 1989 Apr;66(4):319–329. doi: 10.1111/j.1365-2672.1989.tb02485.x. [DOI] [PubMed] [Google Scholar]
  18. Walker D. H., Jr, Anderson T. F. Morphological variants of coliphage P1. J Virol. 1970 Jun;5(6):765–782. doi: 10.1128/jvi.5.6.765-782.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ye Q. Z., Liu J., Walsh C. T. p-Aminobenzoate synthesis in Escherichia coli: purification and characterization of PabB as aminodeoxychorismate synthase and enzyme X as aminodeoxychorismate lyase. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9391–9395. doi: 10.1073/pnas.87.23.9391. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES