Boston University Libraries OpenBU
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    •   OpenBU
    • College of Engineering
    • Biomedical Engineering
    • ENG: Biomedical Engineering: Scholarly Papers
    • View Item
    •   OpenBU
    • College of Engineering
    • Biomedical Engineering
    • ENG: Biomedical Engineering: Scholarly Papers
    • View Item

    Gyrase Inhibitors Induce an Oxidative Damage Cellular Death Pathway in Escherichia Coli

    Thumbnail
    Date Issued
    2007-03-13
    Publisher Version
    10.1038/msb4100135
    Author(s)
    Dwyer, Daniel J.
    Kohanski, Michael A.
    Hayete, Boris
    Collins, James J.
    Share to FacebookShare to TwitterShare by Email
    Export Citation
    Download to BibTex
    Download to EndNote/RefMan (RIS)
    Metadata
    Show full item record
    Permanent Link
    https://hdl.handle.net/2144/3018
    Citation (published version)
    Dwyer, Daniel J, Michael A Kohanski, Boris Hayete, James J Collins. "Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli" Molecular Systems Biology 3:91. (2007)
    Abstract
    Modulation of bacterial chromosomal supercoiling is a function of DNA gyrase-catalyzed strand breakage and rejoining. This reaction is exploited by both antibiotic and proteic gyrase inhibitors, which trap the gyrase molecule at the DNA cleavage stage. Owing to this interaction, double-stranded DNA breaks are introduced and replication machinery is arrested at blocked replication forks. This immediately results in bacteriostasis and ultimately induces cell death. Here we demonstrate, through a series of phenotypic and gene expression analyses, that superoxide and hydroxyl radical oxidative species are generated following gyrase poisoning and play an important role in cell killing by gyrase inhibitors. We show that superoxide-mediated oxidation of iron–sulfur clusters promotes a breakdown of iron regulatory dynamics; in turn, iron misregulation drives the generation of highly destructive hydroxyl radicals via the Fenton reaction. Importantly, our data reveal that blockage of hydroxyl radical formation increases the survival of gyrase-poisoned cells. Together, this series of biochemical reactions appears to compose a maladaptive response, that serves to amplify the primary effect of gyrase inhibition by oxidatively damaging DNA, proteins and lipids.
    Collections
    • ENG: Biomedical Engineering: Scholarly Papers [295]
    • Center for Advanced Biotechnology Papers [9]
    • Center for Biodynamics Papers [8]
    • ENG: Bioinformatics: Scholarly Papers [101]
    • Molecular Biology, Cell Biology and Biochemistry Program: Scholarly Papers [10]


    Boston University
    Contact Us | Send Feedback | Help
     

     

    Browse

    All of OpenBUCommunities & CollectionsIssue DateAuthorsTitlesSubjectsThis CollectionIssue DateAuthorsTitlesSubjects

    Deposit Materials

    LoginNon-BU Registration

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Boston University
    Contact Us | Send Feedback | Help