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dc.contributor.advisorKnodler, Leigh
dc.creatorKlein, Jessica Abbey
dc.date.accessioned2019-08-21T18:13:35Z
dc.date.available2019-08-21T18:13:35Z
dc.date.issued2018
dc.identifier.urihttp://hdl.handle.net/2376/16408
dc.descriptionThesis (Ph.D.), Immunology and Infectious Diseases, Washington State Universityen_US
dc.description.abstractIntracellular pathogens either reside within host-derived vacuoles or escape this compartment to inhabit the cytosol. Why some bacteria lyse their internalization vacuole and others cannot remains enigmatic in Gram-negative bacteria. One prevalent virulence factor Gram-negative pathogens possess is the type III injectisome, a molecular syringe that translocates bacterial proteins into target host cells. Several pathogens, including Salmonella, require this injectisome to invade epithelial cells. Though classically regarded as a vacuolar pathogen, a subset of Salmonella escape the vacuole in epithelial cells and proliferate in the cytosol. We hypothesized that the invasion-associated injectisome also influences intracellular residence of Salmonella. To overcome the dependency of bacterial internalization on the invasion-associated injectisome, we used two genetic approaches. First, we genetically replaced the injectisome proteins that directly interface with host cell membranes with those from related bacteria that have diverse intracellular lifestyles. This led to the identification of orthologs that restore Salmonella invasion, but alter the efficiency of nascent vacuole escape. We also genetically engineered a chemically inducible injectisome that complements Salmonella invasion, but is non-functional once bacteria have entered host cells. This strain implicated the invasion-associated injectisome in cytosolic proliferation of Salmonella, specifically through the actions of two type III effectors. Altogether, these genetic tools have identified that the invasion-associated injectisome is required for multiple intracellular steps in the Salmonella infectious cycle - escape from the internalization vacuole, cytosolic proliferation and cellular egress.en_US
dc.description.sponsorshipWashington State University, Immunology and Infectious Diseasesen_US
dc.languageEnglish
dc.rightsIn copyright
dc.rightsPublicly accessible
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectMicrobiology
dc.subjectbacterial genetics
dc.subjectinjectisome
dc.subjectintracellular bacteria
dc.subjectInv/Mxi-Spa
dc.subjectSalmonella
dc.subjectType III Secretion
dc.titleIdentifying intracellular roles of the Salmonella invasion-associated injectisome
dc.typeElectronic Thesis or Dissertation


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