owing to essential role in bacterial survival, dna gyrase has been exploited as a validated drug target. however, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. here, an attempt has been made to identify new drug-like molecules for shigella flexneri ...

DNA gyrase negatively supercoils DNA. When the requisite breaking and resealing of the DNA are uncoupled by gyrase inhibitors, the DNA becomes cleaved at specific sites. ATP, the cofactor for supercoiling, changes the sites of DNA cleavage. The mechanism of this effect was studied at sites in ColEl and @X174 DNA at which ATP strikingly enhanced cleavage. The following results showed that this i...

Quinolone resistance normally arises by mutations in the chromosomal genes for type II topoisomerases and by changes in the expression of proteins that control the accumulation of quinolones inside bacteria. A novel mechanism of plasmid-mediated quinolone resistance was recently reported that involves DNA gyrase protection by a pentapeptide repeat family member called Qnr. This family includes ...

conclusions this study demonstrated the specificity and sensitivity of the pcr-sscp method for finding mutations in the gyra gene. due to the sensitivity of most isolates to ciprofloxacin, this antibiotic should be considered an appropriate drug for the treatment of related diseases. background during the past several years, nontuberculous mycobacteria (ntm) have been reported as some of the mo...

Genetic and biochemical studies on enzymes known to be involved in regulating DNA supercoiling yield a complex spectrum of effects on the Escherichia coli SOS system. Previous studies indicated that only inhibition of DNA gyrase by antibiotics that act on the DNA gyrase A subunit results in turning on the E. coli SOS system. Here we show that coumermycin, an antibiotic that acts on the DNA gyra...

the broad consumption of antibiotics such as fluoroquinolones and the genetic adaption of opportunistic pathogenic bacteria including pseudomonas aeruginosa , has led to develop of floroquinolone-resistant strains of pseudomonas aeruginosa . thus, the aim of the present study is to reveal the types of hot spot mutations occurring in selected dna gyrase subunit a gene in fluoroquinolone-resistan...

Binding of the quinolone drug norfloxacin to gyrase and DNA has been investigated. We have detected binding to gyrase-DNA complex but find no significant binding to either gyrase or DNA alone. Enzyme containing gyrase A protein with the mutation Ser-83 to Trp (conferring quinolone resistance) showed greatly reduced drug binding.

DNA topoisomerases are important targets in anticancer and antibacterial therapy because drugs can initiate cell death by stabilizing the transient covalent topoisomerase-DNA complex. In this study, we employed a method that uses CsCl density gradient centrifugation to separate unbound from DNA-bound GyrA/ParC in Escherichia coli cell lysates after quinolone treatment, allowing antibody detecti...

Mycobacterium tuberculosis encodes only a single type II topoisomerase, gyrase. As a result, this enzyme likely carries out the cellular functions normally performed by canonical gyrase and topoisomerase IV, both in front of and behind the replication fork. In addition, it is the sole target for quinolone antibacterials in this species. Because quinolone-induced DNA strand breaks generated on p...

ATP-dependent DNA supercoiling catalyzed by Escherichia coli DNA gyrase was inhibited by oxolinic acid, a compound similar to but more potent than nalidixic acid and a known inhibitor of DNA replication in E. coli. The supercoiling activity of DNA gyrase purified from nalidixic acid-resistant mutant (nalA(R)) bacteria was resistant to oxolinic acid. Thus, the nalA locus is responsible for a sec...