Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.
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TLDR
Known gyrase-specific drugs and toxins are reviewed and the prospects for developing new antibacterials targeted to this enzyme are assessed.Abstract:
DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.read more
Citations
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Journal ArticleDOI
Synthesis and investigation of binding interactions of 1,4-benzoxazine derivatives on topoisomerase IV in Acinetobacter baumannii.
TL;DR: 13 compounds were synthesized as 1,4-benzoxazine derivatives which act as bacterial topoisomerase II inhibitors and their antibacterial activities were determined against multi-drug resistant Acinetobacter strains which have ciprofloxacin resistant and GyrA mutation.
Journal ArticleDOI
Diversity and Functions of Type II Topoisomerases.
Dmitry Sutormin,Alina Kh. Galivondzhyan,Alexander V. Polkhovskiy,Sofia O. Kamalyan,Konstantin Severinov,Svetlana Dubiley +5 more
TL;DR: Topoisomerases as mentioned in this paper are enzymes that disentangle the topological challenges associated with supercoiling of the DNA double helix, and resolve catenanes and knots.
Dissertation
New antimicrobials to target gut and food pathogens
TL;DR: It was concluded that S. epidermidis has no specific genomic features to colonise different body sites but is likely to adapt its metabolism to the different conditions, which demonstrates that fermented food and gut environments are valuable sources of new isolates that can yield new antimicrobials.
Journal ArticleDOI
IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria.
Sujin Lee,Jueng Soo You,Amal Gharbi,Yong Joo Kim,Mi Suk Lee,Donghwan Kim,Keun Woo Lee,In Duk Jung,Yeong Min Park +8 more
TL;DR: In this paper, 8-hydroxyquinoline-5-carboxylic acid (IOX1) has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii.
Book ChapterDOI
Antibiotics That Inhibit Nucleic Acid Synthesis
TL;DR: Antibiotics that inhibit synthesis of nucleic acids including DNA and RNA are presented and Mechanisms of action of these drugs and resistance development against them are discussed.
References
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Journal ArticleDOI
DNA topoisomerases: structure, function, and mechanism.
TL;DR: Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
Journal ArticleDOI
A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics
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Journal ArticleDOI
How antibiotics kill bacteria: from targets to networks
TL;DR: The multilayered effects of drug–target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing are discussed.
Journal ArticleDOI
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
TL;DR: This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors and discusses the common mechanism of action ofTopoisomerase poisons by interfacial inhibition and trapping of topisomerase cleavage complexes.
Journal ArticleDOI
Quinolone resistance from a transferable plasmid
TL;DR: Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation, suggesting that a multiresistance plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.
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