Abstract
The electrical potential difference (delta psi) across the membrane of Escherichia coli was measured by the distribution of lipid-soluble cations and correlated with resistance to dihydrostreptomycin, where resistance is presumed due to reduced uptake of the drug. A good correlation between the two measured parameters was found under all conditions tested, which included effects of several mutations, inhibitors, changes in pH, and osmolarity. The most dramatic changes were seen when pH was varied; in wild-type strains resistance increased more than 100-fold, and delta psi fell by 70 mV when pH was reduced from 8.5 to 5.5. These results were interpreted as support for a model in which the uptake of the polycationic aminoglycosides is electrogenic and therefore driven by delta psi. The factor common to mutations and conditions which increase resistance was a reduction in delta psi. A simple model was developed which relates the minimal inhibitory concentration to the rate of aminoglycoside uptake and the rate of growth.
MeSH Terms
2,4-Dinitrophenol
Aminoglycosides/pharmacology
Anti-Bacterial Agents/pharmacology
Cell Membrane/physiology
Dihydrostreptomycin Sulfate/pharmacology
Dinitrophenols/pharmacology
Drug Resistance, Microbial
Escherichia coli/drug effects,ultrastructure
Membrane Potentials
Microbial Sensitivity Tests
Chemicals
Aminoglycosides
Anti-Bacterial Agents
Dinitrophenols
2,4-Dinitrophenol
Dihydrostreptomycin Sulfate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Damper P D
Epstein W
References (26)
26 references, click to expand
-
The measurement of membrane potential and deltapH in cells, organelles, and vesicles.
Methods Enzymol. 1979;55:547-69
PMID: 37402
-
Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: Clostridium perfringens and Bacteroides fragilis.
Antimicrob Agents Chemother. 1979 Jan;15(1):7-13
PMID: 218500
-
Aminoglycoside-resistant mutation of Pseudomonas aeruginosa defective in cytochrome c552 and nitrate reductase.
Antimicrob Agents Chemother. 1980 Jan;17(1):71-9
PMID: 6243453
-
Quantitative measurements of membrane potential in Escherichia coli.
Biochemistry. 1980 Jul 22;19(15):3585-90
PMID: 6996707
-
Linkage map of Escherichia coli K-12, edition 6.
Microbiol Rev. 1980 Mar;44(1):1-56
PMID: 6997720
-
Relation of aerobiosis and ionic strength to the uptake of dihydrostreptomycin in Escherichia coli.
Biochim Biophys Acta. 1980 Nov 5;593(1):1-10
PMID: 6159001
-
Active transport in membrane vesicles from Escherichia coli: the electrochemical proton gradient alters the distribution of the lac carrier between two different kinetic states.
Biochemistry. 1980 Dec 9;19(25):5692-702
PMID: 7006690
-
Chemiosmotic coupling in oxidative and photosynthetic phosphorylation.
Biol Rev Camb Philos Soc. 1966 Aug;41(3):445-502
PMID: 5329743
-
Hemin-deficient mutants of Escherichia coli K-12.
J Bacteriol. 1968 Aug;96(2):570-2
PMID: 4877132
-
Linear sequential arrangement of genes for the biosynthetic pathway of protoheme in Staphylococcus aureus.
Proc Natl Acad Sci U S A. 1968 Dec;61(4):1392-8
PMID: 4236816
-
Vitamin K-deficient mutants of bacteria.
Nature. 1969 Oct 18;224(5216):272
PMID: 5344605
-
Effect of salt concentration on the apparent in-vitro susceptibility of Pseudomonas and other gram-negative bacilli to gentamicin.
J Infect Dis. 1971 Dec;124 Suppl:S59-64
PMID: 5001630
-
Oxidative phosphorylation in Escherichia coli K12. Mutations affecting magnesium ion- or calcium ion-stimulated adenosine triphosphatase.
Biochem J. 1971 Aug;124(1):75-81
PMID: 4256722
-
Potassium transport loci in Escherichia coli K-12.
J Bacteriol. 1971 Nov;108(2):639-44
PMID: 4942756
-
Mechanisms of antibiotic resistance in bacteria.
Annu Rev Biochem. 1973;42:471-506
PMID: 4581231
-
Beta-galactoside transport and proton movements in an adenosine triphosphatase-deficient mutant of Escherichia coli.
Biochem Biophys Res Commun. 1973 Aug 21;53(4):1289-96
PMID: 4270657
-
Use of neomycin in the isolation of mutants blocked in energy conservation in Escherichia coli.
J Bacteriol. 1972 Jul;111(1):287-9
PMID: 4273171
-
Impairment and restoration of the energized state in membrane vesicles of a mutant of Escherichia coli lacking adenosine triphosphatase.
J Biol Chem. 1974 Jul 25;249(14):4587-93
PMID: 4276462
-
The proton electrochemical gradient in Escherichia coli cells.
Eur J Biochem. 1976 Apr 1;63(2):533-41
PMID: 4325
-
Multiple-aminoglycoside-resistant mutants of Bacillus subtilis deficient in accumulation of kanamycin.
Antimicrob Agents Chemother. 1976 Feb;9(2):251-9
PMID: 817658
-
Streptomycin accumulation in susceptible and resistant strains of Escherichia coli and Pseudomonas aeruginosa.
Antimicrob Agents Chemother. 1976 Jun;9(6):928-38
PMID: 820248
-
Gentamicin resistance in clinical-isolates of Pseudomonas aeruginosa associated with diminished gentamicin accumulation and no detectable enzymatic modification.
J Antibiot (Tokyo). 1976 Jul;29(7):743-53
PMID: 821904
-
Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria.
Antimicrob Agents Chemother. 1977 Aug;12(2):163-77
PMID: 143238
-
Streptomycin uptake via an inducible polyamine transport system in Escherichia coli.
Eur J Biochem. 1978 May 16;86(2):345-51
PMID: 207523
-
Proton electrochemical gradient in Escherichia coli cells and its relation to active transport of lactose.
Biochemistry. 1979 Feb 20;18(4):669-73
PMID: 33700
-
Membrane adenosine triphosphatases of prokaryotic cells.
Annu Rev Biochem. 1979;48:103-31
PMID: 157712