scholarly journals Mode of action of GR122222X, a novel inhibitor of bacterial DNA gyrase.

1996 ◽  
Vol 40 (2) ◽  
pp. 473-476 ◽  
Author(s):  
M Oram ◽  
B Dosanjh ◽  
N A Gormley ◽  
C V Smith ◽  
L M Fisher ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Mode Of Action ◽  
Potent Inhibitor ◽  
Dna Gyrase ◽  
Bacterial Dna ◽  
B Subunit ◽  
Terminal Fragment

GR122222X is a potent inhibitor of the supercoiling reaction of bacterial DNA gyrase. We show that this compound binds stoichiometrically to inactivate the ATPase activity of a 43-kDa N-terminal fragment of the B subunit and competitively inhibits the binding of a radiolabelled coumarin drug to N-terminal fragments of GyrB. These and other data suggest that GR122222X has a mode of action similar, but not identical, to that of coumarin antibiotics.

scholarly journals Mode of action of closthioamide: the first member of the polythioamide class of bacterial DNA gyrase inhibitors

2015 ◽  
Vol 70 (9) ◽  
pp. 2576-2588 ◽  
Author(s):  
Alina Iulia Chiriac ◽  
Florian Kloss ◽  
Jonas Krämer ◽  
Cuong Vuong ◽  
Christian Hertweck ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Dna Gyrase ◽  
Bacterial Dna ◽  
Gyrase Inhibitors

scholarly journals In VitroandIn VivoCharacterization of the Novel Oxabicyclooctane-Linked Bacterial Topoisomerase Inhibitor AM-8722, a Selective, Potent Inhibitor of Bacterial DNA Gyrase

2016 ◽  
Vol 60 (8) ◽  
pp. 4830-4839 ◽  
Author(s):  
Christopher M. Tan ◽  
Charles J. Gill ◽  
Jin Wu ◽  
Nathalie Toussaint ◽  
Jingjun Yin ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antibacterial Agents ◽  
Cell Activity ◽  
Dna Gyrase ◽  
Topoisomerase Iv ◽  
Bacterial Dna ◽  
Whole Cell ◽  
Content Type

ABSTRACTOxabicyclooctane-linked novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of recently described antibacterial agents with broad-spectrum activity. NBTIs dually inhibit the clinically validated bacterial targets DNA gyrase and topoisomerase IV and have been shown to bind distinctly from known classes of antibacterial agents directed against these targets. Herein we report the molecular, cellular, andin vivocharacterization of AM-8722 as a representative N-alkylated-1,5-naphthyridone left-hand-side-substituted NBTI. Consistent with its mode of action, macromolecular labeling studies revealed a specific effect of AM-8722 to dose dependently inhibit bacterial DNA synthesis. AM-8722 displayed greater intrinsic enzymatic potency than levofloxacin versus both DNA gyrase and topoisomerase IV fromStaphylococcus aureusandEscherichia coliand displayed selectivity against human topoisomerase II. AM-8722 was rapidly bactericidal and exhibited whole-cell activity versus a range of Gram-negative and Gram-positive organisms, with no whole-cell potency shift due to the presence of DNA or human serum. Frequency-of-resistance studies demonstrated an acceptable rate of resistance emergencein vitroat concentrations 16- to 32-fold the MIC. AM-8722 displayed acceptable pharmacokinetic properties and was shown to be efficacious in mouse models of bacterial septicemia. Overall, AM-8722 is a selective and potent NBTI that displays broad-spectrum antimicrobial activityin vitroandin vivo.

Changed properties of the A subunit in DNA gyrase with a B subunit mutation

1982 ◽  
Vol 186 (4) ◽  
pp. 572-574 ◽  
Author(s):  
E. S. Bogdanova ◽  
S. M. Mirkin ◽  
Zh. G. Shmerling
Keyword(s):  
Dna Gyrase ◽  
B Subunit ◽  
A Subunit

scholarly journals Impact of Amino Acid Substitutions in B Subunit of DNA Gyrase in Mycobacterium leprae on Fluoroquinolone Resistance

2012 ◽  
Vol 6 (10) ◽  
pp. e1838 ◽  
Author(s):  
Kazumasa Yokoyama ◽  
Hyun Kim ◽  
Tetsu Mukai ◽  
Masanori Matsuoka ◽  
Chie Nakajima ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mycobacterium Leprae ◽  
Dna Gyrase ◽  
Fluoroquinolone Resistance ◽  
Amino Acid Substitutions ◽  
B Subunit

scholarly journals Identifikasi Pseudomonas aeruginosa dan tes sensitivitas siprofloksasin pada abses periodontal Identification of Pseudomonas aeruginosa and sensitivity test of ciprofloxacin on periodontal abcess

2011 ◽  
Vol 10 (3) ◽  
pp. 151 ◽  
Author(s):  
Irene E. Rieuwpassa ◽  
Muliaty Yunus ◽  
I Wayan Suka Arsana
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Observational Study ◽  
Broad Spectrum ◽  
Host Resistance ◽  
Dna Gyrase ◽  
Common Type ◽  
Sensitivity Test ◽  
Bacterial Dna ◽  
Resistance Factors ◽  
Synthetic Drug

Periodontitis is a common type of periodontal disease caused by expansion of the early stages of gingivalinflammation. Expansion of inflammation to the tissue structures supporting the teeth can be modified by thepathogenic ability of plaque or host resistance factors. A total of 200 different bacteria have been identified on theplaque. Resistance to antimicrobials can be natural because the microbes develop mechanisms to defendthemselves. Ciprofloxacin is a synthetic drug of the second generation quinolones derivatives. Mechanism of itsaction is to inhibit the activity of bacterial DNA gyrase, which is bactericidal with a broad spectrum against Grampositiveor negative. This observational study identified P. aeruginosa and sensitivity test was performed tociprofloxacin in periodontal abscesses. Study conducted in 23 patients with periodontal abscess. Of those,Pseudomonas was acquired for 8 samples and 4 of them was resistant to ciprofloxacin.

scholarly journals Molecular Cloning of Apicoplast-Targeted Plasmodium falciparum DNA Gyrase Genes: Unique Intrinsic ATPase Activity and ATP-Independent Dimerization of PfGyrB Subunit

2007 ◽  
Vol 6 (3) ◽  
pp. 398-412 ◽  
Author(s):  
Mohd Ashraf Dar ◽  
Atul Sharma ◽  
Neelima Mondal ◽  
Suman Kumar Dhar
Keyword(s):  
Plasmodium Falciparum ◽  
Atpase Activity ◽  
Dna Cleavage ◽  
Functional Characterization ◽  
Dna Gyrase ◽  
Heptad Repeat ◽  
Malarial Parasite ◽  
Temperature Sensitive ◽  
Linear Pattern ◽  
Gyrase A

ABSTRACT DNA gyrase, a typical type II topoisomerase that can introduce negative supercoils in DNA, is essential for replication and transcription in prokaryotes. The apicomplexan parasite Plasmodium falciparum contains the genes for both gyrase A and gyrase B in its genome. Due to the large sizes of both proteins and the unusual codon usage of the highly AT-rich P. falciparum gyrA (PfgyrA) and PfgyrB genes, it has so far been impossible to characterize these proteins, which could be excellent drug targets. Here, we report the cloning, expression, and functional characterization of full-length PfGyrB and functional domains of PfGyrA. Unlike Escherichia coli GyrB, PfGyrB shows strong intrinsic ATPase activity and follows a linear pattern of ATP hydrolysis characteristic of dimer formation in the absence of ATP analogues. These unique features have not been reported for any known gyrase so far. The PfgyrB gene complemented the E. coli gyrase temperature-sensitive strain, and, together with the N-terminal domain of PfGyrA, it showed typical DNA cleavage activity. Furthermore, PfGyrA contains a unique leucine heptad repeat that might be responsible for dimerization. These results confirm the presence of DNA gyrase in eukaryotes and confer great potential for drug development and organelle DNA replication in the deadliest human malarial parasite, P. falciparum.

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