Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1988 Aug;32(8):1187–1191. doi: 10.1128/aac.32.8.1187

Endogenous active efflux of norfloxacin in susceptible Escherichia coli.

S P Cohen 1, D C Hooper 1, J S Wolfson 1, K S Souza 1, L M McMurry 1, S B Levy 1
PMCID: PMC172374  PMID: 3056253

Abstract

Escherichia coli was shown to have an energy-dependent reduced uptake of the fluoroquinolone antimicrobial agent norfloxacin. Studies of everted inner membrane vesicles suggested that this reduced accumulation involved a carrier-mediated norfloxacin active efflux generated by proton motive force with an apparent Km of 0.2 mM and a Vmax of 3 nmol min-1 mg of protein-1. Other hydrophilic, but not hydrophobic, quinolones competed with norfloxacin for transport. Porin (OmpF)-deficient E. coli cells were twofold less susceptible to norfloxacin and showed twice as much energy-dependent reduction in drug uptake. However, active efflux assayed in everted vesicles from the OmpF strain was unchanged compared with that in the parental strain. These findings suggest that in the OmpF mutant decreased outer membrane permeability, combined with active efflux across the inner membrane, in some manner results in decreased steady-state uptake of norfloxacin and lowered drug susceptibility.

Full text

PDF
1187

Selected References

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

  1. Aoyama H., Sato K., Kato T., Hirai K., Mitsuhashi S. Norfloxacin resistance in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother. 1987 Oct;31(10):1640–1641. doi: 10.1128/aac.31.10.1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bedard J., Wong S., Bryan L. E. Accumulation of enoxacin by Escherichia coli and Bacillus subtilis. Antimicrob Agents Chemother. 1987 Sep;31(9):1348–1354. doi: 10.1128/aac.31.9.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Dano K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta. 1973 Oct 25;323(3):466–483. doi: 10.1016/0005-2736(73)90191-0. [DOI] [PubMed] [Google Scholar]
  5. Fojo A. T., Ueda K., Slamon D. J., Poplack D. G., Gottesman M. M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. doi: 10.1073/pnas.84.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. George A. M., Levy S. B. Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. J Bacteriol. 1983 Aug;155(2):531–540. doi: 10.1128/jb.155.2.531-540.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hall M. N., Silhavy T. J. The ompB locus and the regulation of the major outer membrane porin proteins of Escherichia coli K12. J Mol Biol. 1981 Feb 15;146(1):23–43. doi: 10.1016/0022-2836(81)90364-8. [DOI] [PubMed] [Google Scholar]
  8. Hirai K., Aoyama H., Irikura T., Iyobe S., Mitsuhashi S. Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob Agents Chemother. 1986 Mar;29(3):535–538. doi: 10.1128/aac.29.3.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hirai K., Aoyama H., Suzue S., Irikura T., Iyobe S., Mitsuhashi S. Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrob Agents Chemother. 1986 Aug;30(2):248–253. doi: 10.1128/aac.30.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hooper D. C., Wolfson J. S., Souza K. S., Tung C., McHugh G. L., Swartz M. N. Genetic and biochemical characterization of norfloxacin resistance in Escherichia coli. Antimicrob Agents Chemother. 1986 Apr;29(4):639–644. doi: 10.1128/aac.29.4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hooper D. C., Wolfson J. S. The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother. 1985 Nov;28(5):716–721. doi: 10.1128/aac.28.5.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kessel D., Wilberding C. Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists. Cancer Res. 1985 Apr;45(4):1687–1691. [PubMed] [Google Scholar]
  13. 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]
  14. Lundrigan M., Earhart C. F. Reduction in three iron-regulated outer membrane proteins and protein a by the Escherichia coli K-12 perA mutation. J Bacteriol. 1981 May;146(2):804–807. doi: 10.1128/jb.146.2.804-807.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin S. K., Oduola A. M., Milhous W. K. Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science. 1987 Feb 20;235(4791):899–901. doi: 10.1126/science.3544220. [DOI] [PubMed] [Google Scholar]
  16. McMurry L. M., Aronson D. A., Levy S. B. Susceptible Escherichia coli cells can actively excrete tetracyclines. Antimicrob Agents Chemother. 1983 Oct;24(4):544–551. doi: 10.1128/aac.24.4.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McMurry L., Petrucci R. E., Jr, Levy S. B. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3974–3977. doi: 10.1073/pnas.77.7.3974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mobley H. L., Rosen B. P. Energetics of plasmid-mediated arsenate resistance in Escherichia coli. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6119–6122. doi: 10.1073/pnas.79.20.6119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perlin D. S., San Francisco M. J., Slayman C. W., Rosen B. P. H+/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch Biochem Biophys. 1986 Jul;248(1):53–61. doi: 10.1016/0003-9861(86)90400-5. [DOI] [PubMed] [Google Scholar]
  20. Silver S., Keach D. Energy-dependent arsenate efflux: the mechanism of plasmid-mediated resistance. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6114–6118. doi: 10.1073/pnas.79.20.6114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Winkler H. H., Wilson T. H. The role of energy coupling in the transport of beta-galactosides by Escherichia coli. J Biol Chem. 1966 May 25;241(10):2200–2211. [PubMed] [Google Scholar]
  22. Wolfson J. S., Hooper D. C. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985 Oct;28(4):581–586. doi: 10.1128/aac.28.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES