DNA gyrase, topoisomerase IV, and the 4-quinolones - PubMed (original) (raw)

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DNA gyrase, topoisomerase IV, and the 4-quinolones

K Drlica et al. Microbiol Mol Biol Rev. 1997 Sep.

Abstract

For many years, DNA gyrase was thought to be responsible both for unlinking replicated daughter chromosomes and for controlling negative superhelical tension in bacterial DNA. However, in 1990 a homolog of gyrase, topoisomerase IV, that had a potent decatenating activity was discovered. It is now clear that topoisomerase IV, rather than gyrase, is responsible for decatenation of interlinked chromosomes. Moreover, topoisomerase IV is a target of the 4-quinolones, antibacterial agents that had previously been thought to target only gyrase. The key event in quinolone action is reversible trapping of gyrase-DNA and topoisomerase IV-DNA complexes. Complex formation with gyrase is followed by a rapid, reversible inhibition of DNA synthesis, cessation of growth, and induction of the SOS response. At higher drug concentrations, cell death occurs as double-strand DNA breaks are released from trapped gyrase and/or topoisomerase IV complexes. Repair of quinolone-induced DNA damage occurs largely via recombination pathways. In many gram-negative bacteria, resistance to moderate levels of quinolone arises from mutation of the gyrase A protein and resistance to high levels of quinolone arises from mutation of a second gyrase and/or topoisomerase IV site. For some gram-positive bacteria, the situation is reversed: primary resistance occurs through changes in topoisomerase IV while gyrase changes give additional resistance. Gyrase is also trapped on DNA by lethal gene products of certain large, low-copy-number plasmids. Thus, quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases.

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References

    1. J Bacteriol. 1991 Sep;173(18):5854-60 - PubMed
    1. Mol Microbiol. 1996 Jul;21(1):111-22 - PubMed
    1. Cancer Res. 1993 Dec 15;53(24):5908-14 - PubMed
    1. Antimicrob Agents Chemother. 1988 Aug;32(8):1113-8 - PubMed
    1. J Med Microbiol. 1990 Jan;31(1):65-70 - PubMed

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