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    Roles of Secreted Virulence Factors in Pathogenicity of Haemophilus Influenzae: A Dissertation

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    Authors
    Rosadini, Charles V.
    Faculty Advisor
    Dr. Brian J. Akerley
    Academic Program
    Molecular Genetics and Microbiology
    UMass Chan Affiliations
    Molecular Genetics and Microbiology
    Document Type
    Doctoral Dissertation
    Publication Date
    2011-05-12
    Keywords
    Haemophilus influenzae
    Periplasmic Binding Proteins
    Protein Disulfide-Isomerases
    Virulence Factors
    Amino Acids, Peptides, and Proteins
    Bacteria
    Biological Factors
    Microbiology
    Respiratory System
    
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    Abstract
    Haemophilus influenzae is a pathogenic Gram-negative bacterium that colonizes the upper respiratory tract of humans and can cause otitis media, upper and lower respiratory infections, and meningitis. Factors important for H. influenzae to colonize humans and cause disease are not fully understood. Different bacterial pathogens are armed with virulence mechanisms unique to their specific strategies for interacting with their hosts. Many of the proteins mediating these interactions are secreted and contain disulfide bonds required for function or stability. I postulated that identifying the set of secreted proteins in H. influenzae that require periplasmic disulfide bonds would provide better understanding of this bacterium's pathogenic mechanisms. In this thesis, the periplasmic disulfide bond oxidoreductase protein, DsbA, was found to be essential for colonization and virulence of H. influenzae. Mutants of dsbA were also found to be sensitive to the bactericidal effects of serum. However, the DsbA-dependent proteins important for pathogenesis of this organism have not been previously identified. To find them, putative targets of the periplasmic disulfide bond pathway were identified and examined for factors which might be important for mediating critical virulence aspects. By doing so, novel virulence factors were discovered including those important for heme and zinc acquisition, as well as resistance to complement. Overall, the work presented here provides insight into requirements for H. influenzae to survive within various host environments.
    DOI
    10.13028/4d0p-mp61
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31881
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/4d0p-mp61
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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