Abstract
Changes in the amount of oligopeptide binding protein (OppA) in spontaneous kanamycin-resistant mutants of Escherichia coli were investigated. Among 20 colonies obtained from 10(8) cells cultured in the presence of 20 microgram of kanamycin/ml, 1 colony had no detectable OppA and 7 colonies were mutants with reduced amounts of OppA. Sensitivity of wild-type cells to kanamycin increased slightly by transformation of the oppA gene, but the sensitivity of the mutants increased greatly by the transformation. A mutant with no OppA was found to be a nonsense mutant of the oppA gene at amino acid position 166. In a mutant having a reduced level of OppA, the reduction was due to the decrease in OppA synthesis at the translational level. These mutants were also resistant to other aminoglycoside antibiotics, including streptomycin, neomycin, and isepamicin. Isepamicin uptake activities decreased greatly in these two kinds of mutants. The results support the proposition that aminoglycoside antibiotics are transported into cells by the oligopeptide transport system, and that transport is an important factor for spontaneous resistance to aminoglycoside antibiotics.
MeSH Terms
Amino Acids/analysis
Anti-Bacterial Agents/metabolism,pharmacology
Bacterial Proteins
Biological Transport/genetics
Carrier Proteins/biosynthesis,genetics
Down-Regulation
Escherichia coli/drug effects,genetics
Escherichia coli Proteins
Gentamicins/metabolism
Kanamycin/metabolism,pharmacology
Kanamycin Resistance/genetics
Lipoproteins/biosynthesis,genetics
Mutagenesis
Peptides/metabolism
Polyamines/analysis
Chemicals
Amino Acids
Anti-Bacterial Agents
Bacterial Proteins
Carrier Proteins
Escherichia coli Proteins
Gentamicins
Lipoproteins
OppA protein, E coli
Peptides
Polyamines
oligopeptide-binding protein, bacteria
polyphenylalanine
Kanamycin
isepamicin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kashiwagi K
Faculty of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba 263-8522, Japan.
Tsuhako M H
Sakata K
Saisho T
Igarashi A
da Costa S O
Igarashi K
References (25)
25 references, click to expand
-
Role of the membrane potential in bacterial resistance to aminoglycoside antibiotics.
Antimicrob Agents Chemother. 1981 Dec;20(6):803-8
PMID: 6173015
-
Mutational alterations of either large or small ribosomal subunit for the kanamycin resistance.
Biochem Biophys Res Commun. 1980 Jun 16;94(3):755-62
PMID: 6994728
-
Respiration-dependent uptake of dihydrostreptomycin by Escherichia coli. Its irreversible nature and lack of evidence for a uniport process.
Biochem J. 1985 Jun 1;228(2):505-12
PMID: 2409962
-
Formation of a compensatory polyamine by Escherichia coli polyamine-requiring mutants during growth in the absence of polyamines.
J Bacteriol. 1986 Apr;166(1):128-34
PMID: 3514574
-
Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides.
Proc Natl Acad Sci U S A. 1986 Aug;83(16):6164-8
PMID: 2426712
-
Mechanism of bactericidal action of aminoglycosides.
Microbiol Rev. 1987 Sep;51(3):341-50
PMID: 3312985
-
Adjustment of polyamine contents in Escherichia coli.
J Bacteriol. 1988 Jul;170(7):3131-5
PMID: 3290196
-
Identification of the polyamine-induced protein as a periplasmic oligopeptide binding protein.
J Biol Chem. 1990 May 25;265(15):8387-91
PMID: 2187863
-
Isolation of polyamine transport-deficient mutants of Escherichia coli and cloning of the genes for polyamine transport proteins.
J Biol Chem. 1990 Dec 5;265(34):20893-7
PMID: 2249996
-
Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome.
J Biol Chem. 1991 Nov 5;266(31):20922-7
PMID: 1939141
-
Characteristics of the gene for a spermidine and putrescine transport system that maps at 15 min on the Escherichia coli chromosome.
J Biol Chem. 1991 Nov 5;266(31):20928-33
PMID: 1939142
-
The bactericidal action of streptomycin: membrane permeabilization caused by the insertion of mistranslated proteins into the cytoplasmic membrane of Escherichia coli and subsequent caging of the antibiotic inside the cells due to degradation of these proteins.
J Gen Microbiol. 1992 Mar;138(3):551-61
PMID: 1375623
-
Increase of sensitivity to aminoglycoside antibiotics by polyamine-induced protein (oligopeptide-binding protein) in Escherichia coli.
J Bacteriol. 1992 Jul;174(13):4331-7
PMID: 1624428
-
Characteristics of the operon for a putrescine transport system that maps at 19 minutes on the Escherichia coli chromosome.
J Biol Chem. 1993 Jan 5;268(1):146-52
PMID: 8416922
-
Ribosome modulation factor: stationary growth phase-specific inhibitor of ribosome functions from Escherichia coli.
Biochem Biophys Res Commun. 1995 Sep 14;214(2):410-7
PMID: 7677746
-
Molecular mechanism of polyamine stimulation of the synthesis of oligopeptide-binding protein.
J Biol Chem. 1997 Feb 14;272(7):4058-64
PMID: 9020114
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
Some observations on linkage effects in genetic recombination in Escherichia coli K-12.
J Gen Microbiol. 1954 Oct;11(2):250-60
PMID: 13211981
-
Identification and functional characterization of the protein controlled by the streptomycin-resistant locus in E. coli.
Nature. 1969 Apr 26;222(5191):333-9
PMID: 4181187
-
Dihydrostreptomycin accumulation in E. coli.
Nature. 1974 Oct 11;251(5475):534-6
PMID: 4138210
-
Multiplicity of oligopeptide transport systems in Escherichia coli.
J Bacteriol. 1975 Jun;122(3):1208-15
PMID: 1097395
-
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
-
DNA sequencing with chain-terminating inhibitors.
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
PMID: 271968
-
Streptomycin uptake via an inducible polyamine transport system in Escherichia coli.
Eur J Biochem. 1978 May 16;86(2):345-51
PMID: 207523
-
Structural specificity of the triamines sym-homospermidine and aminopropylcadaverine in stimulating growth of spermidine auxotrophs of Escherichia coli.
Biochem Biophys Res Commun. 1983 Dec 16;117(2):616-22
PMID: 6362672