• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    The Rickettsia Ankyrin Repeat Protein 2 is a type IV secreted effector and co-localizes with markers of the endoplasmic reticulum in mammalian cells

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Lehman_umaryland_0373D_10955.pdf
    Size:
    48.59Mb
    Format:
    PDF
    Download
    Author
    Lehman, Stephanie Shae
    0000-0002-4568-3082
    Advisor
    Azad, Abdu F.
    Date
    2018
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Spotted fever and typhus group Rickettsia species are neglected zoonotic, vector-borne bacteria that cause fatal infections and are distributed worldwide. These pathogens efficiently invade host endothelial cells, rapidly escape the phagosome, and establish an "intracytosolic niche," where they grow to high numbers before cell lysis. Despite more than two decades of research, the mechanisms of rickettsial pathogenesis and cytosolic survival remain poorly understood. A candidate virulence factor, Rickettsia ankyrin repeat protein 2 (RARP-2), is largely conserved in pathogenic strains, absent in non-pathogenic strains, and shows increased expression in the mammalian stage of infection. Based on these observations, we hypothesized that RARP-2 functions to enhance pathogenesis during rickettsial infection in mammals. This study demonstrates that RARP-2 is a cytosolically localized effector that is secreted by the type IV secretion system (T4SS) of Rickettsia species from both the typhus and spotted fever groups in order to modulate host pathways. Analysis of homolog distribution and domains of RARP-2 in 43 Rickettsia spp. allowed for the detailed characterization of the C-terminal ankyrin repeats, an N-terminal putative cysteine protease motif, and a C-terminal secretion signal characterized by disorder and flexibility. R. typhi RARP-2 is maximally expressed during the cytosolic phase of infection, is secreted via the T4SS, and overexpression results in the formation of cytosolic vesicular structures. The virulent R. rickettsii str. Sheila Smith (SS) RARP-2 homolog was observed to have 7 more Ank repeats than the avirulent str. Iowa-RARP-2. While both SS- and Iowa-RARP-2 homologs are secreted by the T4SS, only expression of SS-RARP-2 in the avirulent Iowa strain induced a lytic plaque phenotype characteristic of virulent strains. SS-RARP-2 also induced the formation of vesicular like structures in the host cytoplasm that were composed of ER membranes. Mutation of the putative protease active site of SS-RARP-2 abolished the lytic plaque phenotype but did not eliminate association with host membranes. Characterizing RARP-2 and its cognate secretion system marks a significant advance in our understanding of rickettsial biology during the cytosolic stage of infection, and adds to the collective knowledge of how Ank domains are manipulated by obligate intracellular bacteria to regulate host cells.
    Description
    University of Maryland, Baltimore. Molecular Microbiology and Immunology. Ph.D. 2018
    Keyword
    effector
    pathogens
    T4SS
    Ankyrin Repeat
    Bacteria
    Rickettsia--pathogenicity
    Type IV Secretion Systems
    Virulence Factors
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/7943
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.