• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Chemical biology of bacterial metal acquisition and homeostasis

    Dutter, Brendan Frank
    : https://etd.library.vanderbilt.edu/etd-07222016-123636
    http://hdl.handle.net/1803/13459
    : 2016-07-29

    Abstract

    Metals, such as iron, zinc, and manganese, are required for bacterial function and survival. Bacteria have evolved systems to acquire metals from the environments they inhabit. Pathogenic bacteria must obtain metals from their host and have systems dedicated to liberating and stealing metals from host pools. On the other hand, bacteria in the environment must obtain these nutrients from other organic or inorganic sources. While such metals are essential, in high concentrations, they can be toxic due to their reactive nature and bacteria must also have methods of regulating intracellular concentrations. Staphylococcus aureus is a pathogen of humans and obtains nutrient iron in the form of heme. However, heme is toxic to the bacterium at high concentrations and S. aureus utilizes the HssRS two-component system to sense toxic levels of heme and respond by expressing an efflux pump that alleviates heme toxicity. The specific mechanism by which HssRS senses heme levels is not well understood and a high throughput screen was conducted to identify small molecule activators of HssRS. This project has focused on understanding the mechanisms by which two of the molecules identified from the screen, ‘8882 and ‘3981, activate HssRS. Preliminary work has shown ‘8882 activates HssRS in a heme dependent manner while ‘3981 does not. This project focuses on the elucidation of the mechanisms of action of these molecules by identifying the proteins to which they bind using chemical probes for target identification. In contrast to S. aureus, Streptomyces coelicolor is a nonpathogenic soil bacterium and model actinomycete. Many antibiotics used clinically are derived from actinomycetes and this class of bacteria is recognized as a robust source of bioactive small molecules. The molecule coelichelin, which was proposed from genome data and subsequently identified from culture, is a nonribosomal peptide containing three hydroxamate moieties which strongly bind iron. Progress towards the total synthesis of coelichelin is outlined and future completion of the molecule will allow access to large quantities to be used as a chemical tool for studying metal acquisition pathways.
    Show full item record

    Files in this item

    Icon
    Name:
    Dutter.pdf
    Size:
    8.150Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy