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At least 19 recordsLinked to original sources
PubMed1994

Induction of resistance to novobiocin in the novobiocin-producing organism Streptomyces niveus.

During growth of Streptomyces niveus wild-type in the novobiocin production medium CDM the resistance of mycelia to novobiocin rises from about 25 micrograms/ml to over 200 micrograms/ml. (S. lividans, a novobiocin-sensitive strain, is resistant to approx. 10 micrograms/ml novobiocin.) The initial period of low level resistance extends from the time of inoculation of the culture until approx. 70 h when the culture is still in the growth phase. High level resistance is initiated before the start of novobiocin production and rises rapidly to a maximum level beyond the end of the growth phase. The rise in pH of the unbuffered CDM medium which occurs during S. niveus fermentation was shown not to be the cause of the change in novobiocin resistance. However, mycelia-free CDM from S. niveus cultures expressing high level novobiocin resistance was shown to contain a factor which induced high level novobiocin resistance in germinating S. niveus spores. Kinetic studies revealed that the inducer first appears in the culture medium before the switch to high level resistance begins and reaches its highest concentration before resistance reaches its maximum level.

Culture Media↗
PubMed1995

Expression of novobiocin resistance genes in the novobiocin-producing organism Streptomyces niveus.

RNA isolated at intervals during fermentation from the novobiocin-producing wild-type strain of Streptomyces niveus and from a series of novobiocin-non-producing (Nov-) mutants was hybridized to DNA probes containing sequences which specify novobiocin resistance. The probes were made from inserts contained in the clones pGL101 and pGL103 which increase the level of novobiocin resistance of S. lividans transformants from 10 micrograms ml-1 to 50 micrograms ml-1 and 150 micrograms ml-1, respectively. No hybridization was detected with the pGL101 probe. The pGL103 probe hybridized to RNA extracted during the later stages of growth--a pattern corresponding to the transition from low to high level novobiocin resistance during growth of S. niveus wild-type cultures. Neither probe hybridized to RNA extracted from four Nov- mutants. These mutants showed variable levels of novobiocin resistance but none expressed the high wild-type levels. The authors conclude that expression of the DNA sequence in pGL103 is associated with high level novobiocin resistance.

DNA, Bacterial↗
PubMed1990

Novobiocin-resistance sequences from the novobiocin-producing strain Streptomyces niveus.

Two distinct DNA sequences expressing novobiocin resistance in Streptomyces lividans were cloned from the novobiocin-producing species Streptomyces niveus. Clone pGL101 (5kb) conferred resistance to 50 micrograms ml-1 novobiocin, whereas clones pGL102 and pGL103, which carry the same 6.5kb insert but in opposite orientations, expressed resistance to 150 micrograms ml-1. The cloned inserts from pGL101 and pGL103 failed to hybridize with each other or with the cloned novobiocin-resistant gyrB sequence from Streptomyces sphaeroides. Both probes hybridized strongly with DNA from the novobiocin-producing species S. niveus and S. sphaeroides but no hybridization (pGL103) or very weak hybridization (pGL101) was detected with DNA from the non-producing species S. lividans, Streptomyces griseus and Streptomyces antibioticus. S. niveus contains at least three novobiocin-resistance determinants with the pGL101 and pGL103 cloned sequences specific for novobiocin-producing strains of Streptomyces.

Blotting, Southern↗
PubMed1967

Development of resistance to novobiocin, tetracycline, and a novobiocin-tetracycline combination in Staphylococcus aureus populations.

The antibiotic sensitivity of the individual organisms of a bacterial population was determined to study the comparative rates of development of resistance of Staphylococcus aureus to novobiocin, tetracycline, and to a combination of these antibiotics. Serial subculture of S. aureus with the combination of novobiocin-tetracycline (N-T 2.5:1; the ratio in serum of patients dosed with Panalba) showed a significant retardation of resistance outgrowth compared with subculture in the presence of the antibiotics individually. Increase in organisms resistant to novobiocin seen after one N-T subculture was related to the "concentration gap" between novobiocin and tetracycline. Two additional subcultures with N-T caused little or no increase in organisms resistant to novobiocin, tetracycline, or to the combination. The data suggest that the retardation of further development of resistance was the result of tetracycline inhibition of novobiocin-resistant strains and vice versa.

Drug Resistance, Microbial↗
PubMed1986

Chromatid aberrations in a novobiocin-resistant subline of Chinese hamster V79 cells after exposure to novobiocin.

We examined effects of novobiocin alone or in combination with gamma-irradiation, on the frequencies of chromatid-type aberrations in a novobiocin-resistant subline of Chinese hamster V79 cells (NOVOr-1). NOVOr-1 cells were significantly resistant to novobiocin, as compared to wild-type V79 (WT) cells, with respect to cell survival and DNA synthesis. Survival responses of WT and NOVOr-1 cells to gamma-rays in the range 2-10 Gy differed only slightly and the number of chromatid aberrations produced by irradiation at 1 Gy was fairly comparable in the two cell types. Post-irradiation treatment of cells with novobiocin at concentrations exceeding 200 micrograms/ml significantly increased the number of chromatid gaps plus breaks in WT cells as compared with NOVOr-1 cells. With 200 micrograms/ml the increase was 1.2-fold (t-test, P less than 0.05) and with 400 micrograms/ml, 2.3-fold (P less than 0.01) the number produced in NOVOr-1 cells.

Animals↗
PubMed1988

Inhibition of RNA polymerase I-directed transcription by novobiocin. Potential use of novobiocin as a general inhibitor of eukaryotic transcription initiation.

The effect of novobiocin, a coumarin class antibiotic, on rat ribosomal gene (rDNA) transcription in a fractionated extract derived from adenocarcinoma ascites cells (fraction DE-B) was studied. This drug inhibited transcription of rDNA by blocking initiation of transcription, whereas it had no effect on the elongation of the rRNA transcript. Order of addition experiments indicated that the novobiocin effect was at a step(s) in preinitiation complex formation. Preincubation of fraction DE-B with ATP before exposure to this antibiotic prevented inhibition of rDNA transcription. Since novobiocin has been shown to inhibit RNA polymerases II- and III-directed transcription of linear DNAs by interfering with a step(s) in the initiation reaction, these data suggest that initiation of transcription of all classes of RNA is inhibited by novobiocin by a mechanism independent of its effect on DNA topoisomerase II.

Adenocarcinoma↗
PubMed1989

[Features of glycolysis and pentose phosphate pathway in novobiocin sensitive and novobiocin resistant staphylococci].

Intensity of glycolysis and the pentose phosphate cycle in staphylococci sensitive and resistant to novobiocin was studied. The resistant variants did not practically store lactate and the activity of glycolytic enzymes i.e. hexokinase and aldolase was lowered by 15-20 and 53-59 per cent, respectively. Monoiodoacetate, a glycolysis inhibitor suppressed the glucose oxidation rate by 53.3-66.9 per cent in the sensitive variants and by 16-21.8 per cent in the resistant variants. At the same time it was characteristic of the resistant variants to increase the activity of the pentose phosphate cycle enzymes; glucose-6-phosphate dehydrogenase by 25-38.1 per cent transketolase by 21.5-27.3 per cent and transaldolase by 30-57.1 per cent. No differences in the transhydrogenase reaction kinetics of both the novobiocin sensitive and the novobiocin resistant variants were observed.

Drug Resistance, Microbial↗
PubMed1978

[Separation of novobiocin, isnovobiocin and descarbamyl novobiocin by a thin-layer chromatographic method].

A thin-layer chromatographic method for separation of novobiocin, isonovobiocin and descarbamylnovobiocin using Silufol plates was developed. The method is simple and rapid. It provided clear separation of the components and using of diethyl ether, a simple individual separating solvent. The method allowed determination of novobiocin and the products of its isomerization in the fermentation broth, extracts and dry substances, as well as performance of operative control and regulation of the technological processes of fermentation and chemical purification of novobiocin.

Chromatography, Thin Layer↗
PubMed1989

Interplay of novobiocin-resistant and -sensitive DNA gyrase activities in self-protection of the novobiocin producer, Streptomyces sphaeroides.

The novobiocin (Nb)-producing organism, Streptomyces sphaeroides, possesses two gyrB genes: gyrBS and gyrBR (encoding the DNA gyrase B subunit-the normal target for Nb) whose products differ in their response to the drug. Novobiocin-sensitive gyrase is the predominant form of the enzyme in this strain and is produced constitutively but at variable levels, whereas Nb-resistant gyrase appears when growth takes place in the presence of the drug. The promoter isolated from the Nb-resistance determinant responds sharply to changes in DNA topology, being activated when the (negative) superhelical density is reduced and vice versa when the supercoiling of DNA is increased. Thus, resistance to Nb in S. sphaeroides is induced by a reduction in DNA supercoiling due to the action of autogenous drug on the sensitive gyrase.

Blotting, Southern↗
PubMed1984

Loss of plasmids containing cloned inserts coding for novobiocin resistance or novobiocin sensitivity in Haemophilus influenzae.

Plasmids pNov1 and pNov1s , coding for resistance and sensitivity to novobiocin, respectively, were readily lost from wild-type Haemophilus influenzae but retained in a strain lacking an inducible defective prophage. The plasmid loss could be partly or wholly eliminated by a low-copy-number mutation in the plasmid or by the presence of certain antibiotic resistance markers in the host chromosome. Release of both phage HP1c1 , measured by plaque assay, and defective phage, measured by electron microscopy, was increased when the plasmids were present. The frequency of recombination between pNov1 and the chromosome, causing the plasmid to be converted to pNov1s , could under some circumstances be decreased from the normal 60 to 70% to below 10% by the presence of a kanamycin resistance marker in the chromosome. This suggested that a gene product coded for by the plasmid, the expression of which was affected by the kanamycin resistance marker, was responsible for the high recombination frequency. Evidence was obtained from in vitro experiments that the gene product was a gyrase.

Anaerobiosis↗