Mechanisms of anaerobic nitric oxide detoxification by Salmonella enterica serovar Typhimurium

Arkenberg, Anke (2013) Mechanisms of anaerobic nitric oxide detoxification by Salmonella enterica serovar Typhimurium. Doctoral thesis, University of East Anglia.

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    Abstract

    Salmonella is the cause of millions of food- and water-borne infections
    worldwide. Systemic infection and gastroenteritis are the main diseases and
    often prove fatal to immunocompromised patients.
    Key to Salmonella’s pathogenicity is the survival of several components of the
    innate immune system encountered during infection. Reactive oxygen and
    nitrogen species (ROS and RNS) are an integral part of this antibacterial
    defence of the immune system. Exposure to ROS and RNS occurs within
    phagocytic immune cells such as macrophages, where such generation of
    radicals is used to combat pathogens. NO is a radical belonging to the group of
    RNS that damages bacterial DNA and proteins. Detoxification of NO is essential
    during infection to allow Salmonella to survive and replicate within
    macrophages. Three enzymes are currently known to help Salmonella to
    detoxify NO, but their deletion, however, does not eliminate Salmonella’s
    survival. Therefore, it is predicted that further mechanisms for NO detoxification
    exist.
    In this study, the core NO regulon has been identified: Expression of nine genes
    is significantly increased during endogenous and exogenous NO exposure of S.
    Typhimurium. Their functions range from carbon starvation, cytochrome
    oxidation, iron-sulphur repair and NO reduction to putative proteins with
    unknown function, some of which contain domains for tellurite resistance. Single
    and combination deletion strains have shown that these genes are important to
    decrease anaerobic NO sensitivity of S. Typhimurium and for intracellular
    survival in murine macrophages. Furthermore, we have shown for the first time
    that the core NO regulon also provides protection against tellurite. Tellurite is
    toxic and requires detoxification when encountered. Reducing tellurite to yield
    the elemental tellurium results in the release of ROS, which then need to be
    detoxified further. Deletion strains sensitive to tellurite have also shown
    increased sensitivity to NO. Concurrently, tellurite resistance genes also
    facilitate the defence against NO.

    Item Type: Thesis (Doctoral)
    Faculty \ School: Faculty of Science > School of Biological Sciences
    Depositing User: Mia Reeves
    Date Deposited: 12 Jun 2014 15:06
    Last Modified: 12 Jun 2014 15:06
    URI: https://ueaeprints.uea.ac.uk/id/eprint/48768
    DOI:

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