Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conditions, such as anoxia or glucose starvation, which induce the glucose-regulated set of stress proteins also lead to resistance to adriamycin (J. Shen, C. Hughes, C. Chao, J. Cai, C. Bartels, T. Gessner, and J. Subjeck, Proc. Natl. Acad. Sci. USA 84:3278-3282, 1987) and etoposide. We report here that chronic anoxia, glucose starvation, 2-deoxyglucose, the calcium ionophore A23187, glucosamine, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), and tunicamycin (all specific inducers of the glucose regulated system) lead to a rapid and selective depletion of topoisomerase II from isolated nuclei of Chinese hamster ovary cells. This effect precedes a decline in tritiated thymidine incorporation and a redistribution of cells from S into G1/G0. The depletion of the enzyme is not accompanied by a decline in mRNA levels. We have also examined the mutant Chinese hamster K12 cell line which is temperature sensitive for expression of glucose-regulated proteins. When nuclei were isolated from K12 cells incubated at the nonpermissive temperature, a loss of topoisomerase II was again observed in congruence with the expression of stress proteins and cellular resistance to etoposide. These changes were not obtained in parental Wg1A cells incubated at the same temperature. These studies indicate that topoisomerase II is highly sensitive to glucose-regulated stresses and that its depletion from the nucleus, with the associated changes in cell cycle parameters, may represent general characteristics of the glucose-regulated state. Since anoxia and glucose starvation can occur during tumor development, this pathway for expression of drug resistance may have clinical ramifications.
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PMID:Depletion of topoisomerase II in isolated nuclei during a glucose-regulated stress response. 255 89

Enoxacin inhibits growth of Escherichia coli K12 strains primarily by binding to the GyrA subunit of DNA gyrase (topoisomerase II); strains with gyrA, but not gyrB, mutations are less susceptible to the bactericidal effects of this agent. In sensitive strains, enoxacin completely inhibits DNA synthesis within 5 min and produces drug-gyrase-DNA complexes at numerous sites throughout the E. coli chromosome, as shown by the formation of linear DNA molecules after detergent treatment. Enoxacin, even at subminimal inhibitory concentrations, induces the bacterial SOS system, even in partially resistant gyrA strains. This drug also inhibits the induced expression of the lacZ encoded beta-galactosidase, regardless of whether this gene is located on the chromosome, a low copy number F' plasmid or high copy number Col E1 related plasmids. This inhibition of gene expression at subminimal inhibitory concentrations is likely to be a factor, in addition to gyrase inhibition, in the elimination of Col E1 plasmids and to the reduction in R plasmid conjugal transfer. Enoxacin enhances the bactericidal effects of kanamycin in both in-vitro and in-vivo models, suggesting that this quinolone may be effective in the treatment of infections due to strains resistant to antibacterials as a consequence of plasmid encoded resistance determinants.
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PMID:Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin. 283 13

We have previously shown that Mu restores an active DNA replication at non-permissive temperature in E. coli K12 ligts7 strains. In this paper we describe two new types of phage mutants for the Mu lig function. The Mu ligts mutants are conditional lethals defective for both integration and replication of DNA, unable to 'complement' the bacterial lig mutation; the map between B and lys. The mutants of the other type, on the other hand, are able to restore to a maximum level the activity impaired by the ligts7 mutation in the host. We suggest the hypothesis that the product of Mu lig gene could be part of a complex as a topoisomerase.
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PMID:Two classes of Mu lig mutants: the thermosensitives for integration and replication and the hyperproducers for ligase. 700 31

Activation of efflux systems and the formation of biofilm are majorly adapted by microbes to resist antimicrobial agents. PPEF (bisbenzimidazole) targeting topoisomerase IA is observed to be an effective bactericidal agent against both Gram-positive and Gram-negative bacterial strains and thus can be developed as potent broad-spectrum antibiotic against MDR strains. PPEF treatment did not cause target specific mutation instead it leads to up-regulation of efflux gene in E. coli K12 as a mechanism of resistance. Microscopy, fluorescence spectroscopy and flow cytometry result demonstrate higher accumulation of PPEF in efflux gene deleted E. coli K12 mutants, and also suggest that Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP), resist the efflux of PPEF, and thus increases efficacy of PPEF. Herein, we report, PPEF and CCCP synergistically killed the persistent bacterial cells, which are not killed by PPEF alone. The above two compounds together inhibited biofilm formation, eradicate preformed biofilms and kills the biofilm cells of P. aeruginosa. PPEF and CCCP together reduced bacterial load of E. coli ATCC25922 by 6 log10 in neutropenic thigh infection model of balb/c mice. Present study suggests that combination therapy could be a promising antimicrobial strategy to handle MDR pathogenic strains.
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PMID:Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazone combination against MDR bacterial strains. 2830 97