Dissecting the interactions between Francisella tularensis and its murine host

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Francisella is a gram-negative bacterium that causes tularemia. It is capable of infecting a remarkably broad host range including humans, mammals, birds and fish via multiple different routes of infection, establishing a successful colonization event within the various organs. This facultative, intracellular pathogen is also capable of invading a broad range of host cell types ranging from macrophages to fibroblasts. This is an extremely fascinating facet of the bacterium. The ability of Francisella to infect such a wide range of hosts and cell types suggests that the bacterium either co-opts cellular mechanisms common to all hosts and cell types or has the requisite bacterial genes to adapt to many different intraorganismal environments, or both. We were interested in studying the diverse repertoire of interactions that may occur between the bacterium and its murine host. In this thesis, the transposon site hybridization (TraSH) negative selection strategy was applied in a range of in vivo and in vitro systems to identify novel host-pathogen interactions in Francisella. We subsequently demonstrated that Francisella require tryptophan for virulence specifically in the lungs due to lung-specific induction of a host innate immune molecule indoleamine 2,3-dioxygenase 1. Alveolar macrophages may also deplete intracellular trytophan via a novel mechanism and microbial lung-specific requirement of tryptophan for virulence may be widely applicable to all bacterial species. We also demonstrate that Francisella hypercytotoxic mutants, unlike previously suggested, induce macrophage hypercytotoxicity due to increased bacteriolysis in the intracellular milieu. Identification and characterization of bacterial mutants that are attenuated under different in vitro and in vivo conditions have led to further insights into the interactions that occur between Francisella and its murine host.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2011
Issuance monographic
Language English


Associated with Peng, Kaitian
Associated with Stanford University, Department of Microbiology and Immunology
Primary advisor Monack, Denise M
Thesis advisor Monack, Denise M
Thesis advisor Falkow, Stanley
Thesis advisor Lewis, David
Thesis advisor Schneider, David (David Samuel)
Advisor Falkow, Stanley
Advisor Lewis, David
Advisor Schneider, David (David Samuel)


Genre Theses

Bibliographic information

Statement of responsibility Kaitian Peng.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2011.
Location electronic resource

Access conditions

© 2011 by Kaitian Peng
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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