Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Novobiocin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1986

Novobiocin and rifampicin in combination against methicillin-resistant Staphylococcus aureus: an in-vitro comparison with vancomycin plus rifampicin.

Novobiocin and rifampicin were evaluated in vitro as a possible new antibiotic combination against methicillin-resistant Staphylococcus aureus. An evaluation of 20 strains of methicillin-resistant Staph. aureus using microdilution checkerboard techniques at 10(5) cfu/ml showed neither synergy nor antagonism between novobiocin and rifampicin or between vancomycin and rifampicin. Agar surface inoculation of six strains of methicillin-resistant Staph. aureus showed increased synergy with increased inocula (10(6)-10(9) cfu) for novobiocin plus rifampicin compared to vancomycin plus rifampicin. Time-kill curves showed indifference at 6h for all combinations, whereas, at 24 and 48 h, they generally showed indifference, occasionally synergy, but never antagonism. The 'synergy' between novobiocin and rifampicin at higher inocula of methicillin-resistant Staph. aureus appears to be due to prevention of emergence of resistant organisms and may have clinical relevance. The combination of novobiocin-rifampicin merits further investigation.

Drug Combinations↗
PubMed1987

Mannose inhibition as a significant marker for differentiating among novobiocin-resistant staphylococci of relevance in clinical microbiology.

A specific method for the identification of Staphylococcus saprophyticus among novobiocin-resistant species isolated from man is described. The test is based on novobiocin resistance, non-fermentation of D-mannose and early inhibition with late secondary growth on glucose/mannose + novobiocin agar plates. On this medium novobiocin-resistant Staphylococcus cohnii showed a confluent, continuous and homogeneous growth after 24 h which remained unchanged at 48 h whether or not it fermented D-mannose, whereas novobiocin-resistant Staphylococcus xylosus fermented D-mannose. These results are discussed in relation to a possible causal role of PTS enzymes and phosphomannose isomerase deficiency in mannose inhibition.

Drug Resistance, Microbial↗
PubMed1993

In vitro activity of novobiocin against multiresistant strains of Enterococcus faecium.

Sixty strains of vancomycin- and ampicillin-resistant Enterococcus faecium were evaluated for their susceptibilities to novobiocin in vitro. In Mueller-Hinton broth, novobiocin inhibited all strains when it was used at a concentration of < or = 2 microgram/ml and 40 of 60 strains when it was used at a concentration of < or = 0.5 micrograms/ml. MICs were 8- to 16-fold higher in 50% serum. Novobiocin alone resulted in 2-log-unit killing at 24 h. Combinations of novobiocin and a fluoroquinolone (either ciprofloxacin or ofloxacin) were additive and bactericidal for quinolone-susceptible strains in either broth or 50% serum. Gentamicin did not affect novobiocin activity, and rifampin and doxycycline were antagonistic.

Anti-Infective Agents↗
PubMed1998

Immunomodulating properties of the antibiotic novobiocin in human monocytes.

We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-alpha production by inhibiting translation of the TNF-alpha mRNA. Elevated TNF-alpha levels in mice treated with D-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of gamma-actins.

Animals↗
PubMed2005

Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus.

Coumarin-resistant mutants of Staphylococcus aureus were isolated by three-step selection with novobiocin at different concentrations. Sequencing analysis of the gyrB and parE genes of the first-, second-, and third-step mutants revealed that successive point mutations first occurred specifically in the gyrB gene, followed by a point mutation in the parE gene and then an additional point mutation in the gyrB gene. These findings demonstrate that DNA gyrase is the primary target and that topoisomerase IV is the secondary target for novobiocin and that the accumulation of point mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin in S. aureus. Moreover, our results show that the amino acid substitutions (Asp-89 to Gly and Ser-128 to Leu) found in GyrB are associated with resistance to novobiocin but not to coumermycin A1, suggesting that the interactions of novobiocin and coumermycin A1 with GyrB differ at the molecular level.

Amino Acid Sequence↗
PubMed2004

Influence of prepartum pirlimycin hydrochloride or penicillin-novobiocin therapy on mastitis in heifers during early lactation.

A study was conducted in 2 dairy research herds to determine whether prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride was effective for reducing the percentage of heifers and mammary quarters infected with mastitis pathogens during early lactation. Almost 96% of Jersey heifers (67 of 70) and 71.3% of quarters (199 of 279) were infected 14 d before expected calving. Of the quarters infected at 14 d before expected parturition, 75% (54 of 72) were uninfected following treatment with penicillin-novobiocin; 87% (61 of 70) were uninfected following treatment with pirlimycin, and 56% (32 of 57) were uninfected in the untreated negative control group. The majority of intramammary infections in Jersey heifers were due to coagulase-negative staphylococci (61%), Streptococcus species, primarily Streptococcus uberis (19%), and Staphylococcus aureus (8%). Almost 73% of Holstein heifers (40 of 55) and 34.3% of mammary quarters (73 of 213) were infected 14 d before expected calving. Of the quarters infected at 14 d before expected parturition, 76% (19 of 25) were uninfected following treatment with penicillin-novobiocin; 59% (17 of 29) were uninfected following treatment with pirlimycin, and 26% (5 of 19) were uninfected in the untreated negative control group. The majority of intramammary infections in Holstein heifers were due to coagulase-negative staphylococci (44%) and Staph. aureus (30%). In both herds, the bacteriological cure rate was significantly higher in heifer mammary glands treated with penicillin-novobiocin or pirlimycin hydrochloride than in untreated controls. Prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride significantly reduced the percentage of heifers and quarters infected with mastitis pathogens during early lactation.

Animals↗
PubMed2000

[The role of topoisomerase II in mammalian cells response to ionizing radiation. II. Effect of a small concentration of novobiocin on cell cycle in x-rays irradiated HeLa cells].

Flow cytometry was used to study cell cycle recovery in X-irradiated HeLa cells after the action of novobiocin, an inhibitor of topoisomerase II. A prolonged treatment with 0.4 mM novobiocin (30 h) of intact cells did not affect cell cycle progression. Novobiocin treatment of 5 Gy-irradiated cells resulted in a significant decrease of G2-block, if compared with X-irradiated cells. These data, together with our previous results on the effect of 1 mM novobiocin on cell cycle in X-irradiated CHO K1 cells, allow to suggest an involvement of topoisomerase II in cell response to ionizing radiation. But one cannot exclude a concurrent effect of novobiocin with proteins other than topoisomerase II, for example, with protein p34cdc2-kinase, known to be involved in cell cycle regulation.

Cell Cycle↗
PubMed1990

Alteration of differentiation state of human hepatocytes cultured with novobiocin and butyrate.

Chang liver cells cultured in the simultaneous presence of novobiocin and butyrate stopped proliferating and changed into fibroblast-like cells with remarkably elongated cytoplasm. In these fibroblast-like cells, the cellular content of both protein and DNA was increased 2- to 3-fold. In addition, the production of specific proteins such as type III procollagen, actin, and tubulin was increased and the expression of proliferation-associated nuclear antigen which was reactive with Ki-67 monoclonal antibody was reduced remarkably. Therefore, Chang liver cells cultured with novobiocin and butyrate were considered to be arrested at the premitotic G2 phase of the cell cycle and then enter into the noncycling resting state. These actions of novobiocin and butyrate were not mediated by the pathway of epidermal growth factor action or modulated by the diacylglycerol agonist 1-oleoyl-2-acetylglycerol and the C kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. On the other hand, novobiocin was disclosed to be a stimulator of [3H]acetate uptake and acted synergistically with butyrate in enhancing nuclear protein acetylation. From these results it can be speculated that novobiocin and butyrate chemically modulate nuclear proteins and thereby alter the gene expression and the differentiation state of Chang liver cells.

Acetylation↗
PubMed1987

Novobiocin inhibits Xenopus transcription factor IIIA-DNA interactions.

Novobiocin and coumermycin, inhibitors of the B subunit of Escherichia coli DNA gyrase, inhibit the binding of Xenopus transcription factor IIIA (TFIIIA) to the 5 S RNA gene. Nalidixic acid and oxolinic acid, inhibitors of the A subunit of DNA gyrase, have no effect on the TFIIIA-5 S RNA gene interaction. Novobiocin and coumermycin inhibit TFIIIA-dependent DNA renaturation. Novobiocin dissociates TFIIIA.5 S RNA gene complexes and TFIIIA.5 S RNA complexes (7 S particles). Novobiocin induces TFIIIA aggregation, a phenomenon likely to be responsible for the inhibition of TFIIIA-DNA interactions. Novobiocin inhibition of TFIIIA can be reversed by dilution.

Aminocoumarins↗
PubMed1986

Effect of the virulence associated 47 megadalton plasmid of Yersinia pestis on permeability to gentian violet and sensitivity to novobiocin.

The loss of the 47 megadalton (Mdal) plasmid of Yersinia pestis resulted in increased gentian violet uptake and increased sensitivity to novobiocin. The addition of calcium caused a decrease in gentian violet uptake and a decrease in novobiocin sensitivity independent of the plasmid. Differentiation of cells bearing and lacking the plasmid was accomplished using novobiocin in the presence of calcium at 26 degrees C. The novobiocin resistance levels of cells lacking the 47 Mdal plasmid and cells with the plasmid, but with an insertion in or a deletion in, or encomposing, the calcium dependence region of this plasmid, indicated that the resistance to novobiocin was not associated with the calcium dependence region, but was associated with a separate 47 Mdal plasmid region. Examination of Yersinia pseudotuberculosis and Yersinia enterocolitica isolates demonstrated that functionally similar sites are present on the plasmids that encode for calcium dependence in these species.

Calcium↗
PubMed1984

[Various aspects of regulation of the biosynthesis of novobiocin and exoproteases in cultures of Streptomyces spheroides 35].

Streptomyces spheroides 35, a novobiocin-producing organism, was used in the study. In addition to the antibiotic the culture produces proteases capable of splitting fibrin. Depending on the medium composition and component ratio different amounts of novobiocin and proteases were formed. To show various aspects of the biological interaction of the synthesis of proteolytic enzymes and novobiocin, the studies were performed with chloramphenicol. It was found that the main quantity of free amino acids accumulated in the culture liquid phase, while in the mycelial phase only traces of the amino acids were detected. The regularities of the free amino acid accumulation in the media with novobiocin and chloramphenicol were identical as compared to the control. The excess of novobiocin during the second phase of the culture development was shown to influence the synthesis of nucleic acids, whereas inhibition of protein synthesis was secondary.

Amino Acids↗
PubMed1977

Effects of varying concentrations of novobiocin incorporated into two salmonella plating media on the recovery of four enterobacteriaceae.

Hydrogen sulfide-producing strains of salmonellae, Escherichia coli, Citrobacter freundii, and Proteus mirabilis were isolated from fresh pork sausage. All the strains produced black-centered colonies on Hektoen enteric agar (HE). On xylose lysine deoxycholate agar (XLD), C. freundii produced yellow colonies, and the strains of the other three genera formed black-centered colonies. The selectivity of HE and XLD for salmonellae was improved by the addition of novobiocin to both media. With increasing concentrations of novobiocin, the degree of growth inhibition for the four genera was less on HE than on XLD. Novobiocin concentrations of 80 mug/ml in HE and 5 mug/ml in XLD did not affect the growth or colonial morphology of salmonellae. When 80 mug of novobiocin per ml was incorporated into HE, P. mirabilis strains were not recovered, 40% of C. freundii strains failed to form black-centered colonies, and growth of E. coli strains was not affected but colonies were altered without eliminating the black centers. When novobiocin at 5 mug/ml was incorporated into XLD, colonies of P. mirabilis strains were not recovered, C. freundii formed yellow colonies, and the colonies of the H(2)S-producing E. coli strains were unaffected.

Journal Article↗
PubMed1991

Cisplatin and novobiocin in the treatment of non-small cell lung cancer. A Southwest Oncology Group study.

Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin). One patient remains on study and cannot be evaluated for response. No complete responses were seen. Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response. The median survival time of all patients was just less than 7 months. These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC). Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity. It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.

Administration, Oral↗
PubMed1988

Cloning and characterization of a DNA gyrase B gene from Streptomyces sphaeroides that confers resistance to novobiocin.

A gyrB gene from Streptomyces sphaeroides, a producer of novobiocin, has been cloned in Streptomyces lividans, where it conferred resistance to novobiocin. The Streptomyces gyrB gene was sufficiently similar to a Bacillus subtilis gyrB probe to be specifically recognized during Southern analysis. Partial purification of DNA gyrase by affinity chromatography revealed the presence of two such activities (differing in their responses to novobiocin) in the clone. The product of the cloned gene, a novobiocin-resistant DNA gyrase B subunit, was identified in vitro by coupled transcription--translation as a 79-kd protein.

Cloning, Molecular↗
PubMed1990

The effect of novobiocin on yeast topoisomerase type II.

Low concentrations of novobiocin are toxic to permeable yeast cells, but do not inhibit type II topoisomerase activity. Furthermore, the enzyme does not bind specifically to novobiocin-Sepharose. These observations are in agreement with genetical analyses. Mutations at a single locus that confer novobiocin resistance and temperature sensitivity exhibit a similar phenotype to cells treated with novobiocin, but are not topoisomerase II mutants.

Chromatography, Affinity↗
PubMed1991

cysB and cysE mutants of Escherichia coli K12 show increased resistance to novobiocin.

Mutations in the cysB and cysE genes of Escherichia coli K12 cause an increase in resistance to the gyrase inhibitor novobiocin but not to coumermycin, acriflavine and rifampicin. This unusual relationship was also observed among spontaneous novobiocin resistant (Novr) mutants: 10% of Novr mutants isolated on rich (LA) plates with novobiocin could not grow on minimal plates, and among those approximately half were cysB or cysE mutants. Further analyses demonstrated that cysB and cysE negative alleles neither interfere with transport of novobiocin nor affect DNA supercoiling.

Acetyltransferases↗
PubMed1994

Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells.

The effect of the antibiotic agent novobiocin on the sensitivity of melanoma cells to colchicine and vinblastine was examined in drug-sensitive and drug-resistant B16 melanoma cells. A cell line COL/R was selected for colchicine resistance. The COL/R cell line (resistant to 80 ng/ml colchicine) was found to possess the multidrug-resistant (MDR) phenotype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine accumulation was markedly decreased in COL/R cells as compared to the parental B16 cells. Verapamil reversed drug resistance and increased rhodamine accumulation in COL/R cells. Novobiocin in combination with colchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased colchicine resistance and increased rhodamine accumulation. These data show that novobiocin increases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.

Animals↗
PubMed1990

A DNA topoisomerase II-independent route for novobiocin-mediated resistance to DNA binding agents.

The coumermycin antibiotic novobiocin is currently under investigation as an agent that can modify the toxicity of various anti-cancer drugs, potentially via one of its many pharmacological effects: namely, the interference with type II DNA topoisomerase function. This paper investigates the ability of novobiocin to modify the cellular/nuclear accumulation and toxicity of two types of DNA binding agents (the minor groove ligand Hoechst 33342 and the intercalating anthracycline Adriamycin). We report that novobiocin reduces the cytotoxicity of both agents and that this can be attributed to a reduction in cellular and, consequently, nuclear accumulation of these agents rather than to any effect on cellular export. The antibiotic was also active (at non-toxic concentrations) in delaying the progression of cells into S phase and G2 phase. This potential for novobiocin to effect rescue from toxicity by disturbance of the delivery of a drug to a potentially important intracellular target, together with the provision of an extended period of cellular recovery prior to the commitment of cells to G2 + M phase, should be recognised in the design of combination chemotherapy.

Animals↗