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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Reactive oxygen and nitrogen species in host defence against Francisella tularensis /

Lindgren, Helena, January 2005 (has links)
Diss. (sammanfattning) Umeå : Univ., 2005. / Härtill 4 uppsatser.
2

Examining the regulation of virulence factors in Francisella tularensis

Buchan, Blake Wade. Jones, Bradley D. January 2009 (has links)
Thesis supervisor: Bradley D. Jones. Includes bibliographic references (p. 136-151).
3

Sequencing and functional analysis of a Francisella tularensis pathogenicity island

Zhang, Na. 10 April 2008 (has links)
Francisella tularensis, a Gram-negative coccobacillus, is an extremely virulent intracellular pathogen. Infection of humans with this pathogen results in tularemia, a life-threatening disease. An approximately 35 kb region found in the F. tularensis genome exhibits many features of a pathogenicity island. This region has a lower G+C content than the average G+C content of the F. tularensis genome, and is surrounded by transposable elements. Results from both a previous study and our present study demonstrated that at least four genes located on the Francisella pathogenicity island (FPI) are required for virulence. This represents the first description of a pathogenicity island in F. tularensis. The FPI-encoded proteins, however, have no significant similarities to any known bacterial proteins. Therefore, we believe that the FPI genes may encode a cluster of novel virulence factors, although the mechanism and their characteristics remain to be determined.
4

The occurrence and movement of Fancisella tularensis McCoy and Chapin across landscapes

Blount, Keith Wayne 15 May 2009 (has links)
Tularemia is a one of the most complex zoonotic diseases. Francisella tularensis McCoy and Chapin, the causative agent of tularemia is considered endemic in Texas, but outbreaks are rare and there are few human cases each year. Tularemia is listed as a Category A biological weapon and air samples are taken daily in select major metropolitan areas, including Houston, to monitor for its presence. I determined the potential risk for tularemia introduction and spread in southeast Texas through field surveillance for the pathogen and its major arthropod vector in the region, Amblyomma americanum (L.); completion of a habitat capability map for A. americanum, based on landscape analysis of the study area; and potential movement and long-term establishment of tularemia through development of a spatially explicit, agent-based, simulation model. Field and laboratory investigations resulted in the identification of two samples positive for F. tularensis. A feral cat tested positive for Type B tularemia using a new aptamer-based assay, and one sample returned positive in Amblyomma maculatum by polymerase chain reaction. This work sheds light on a complex host-pathogen-vector interaction in the rural to urban interface and establishes a framework for future tularemia field work and pathogen modeling in the rural to urban interface.
5

The occurrence and movement of Fancisella tularensis McCoy and Chapin across landscapes

Blount, Keith Wayne 15 May 2009 (has links)
Tularemia is a one of the most complex zoonotic diseases. Francisella tularensis McCoy and Chapin, the causative agent of tularemia is considered endemic in Texas, but outbreaks are rare and there are few human cases each year. Tularemia is listed as a Category A biological weapon and air samples are taken daily in select major metropolitan areas, including Houston, to monitor for its presence. I determined the potential risk for tularemia introduction and spread in southeast Texas through field surveillance for the pathogen and its major arthropod vector in the region, Amblyomma americanum (L.); completion of a habitat capability map for A. americanum, based on landscape analysis of the study area; and potential movement and long-term establishment of tularemia through development of a spatially explicit, agent-based, simulation model. Field and laboratory investigations resulted in the identification of two samples positive for F. tularensis. A feral cat tested positive for Type B tularemia using a new aptamer-based assay, and one sample returned positive in Amblyomma maculatum by polymerase chain reaction. This work sheds light on a complex host-pathogen-vector interaction in the rural to urban interface and establishes a framework for future tularemia field work and pathogen modeling in the rural to urban interface.
6

Structural studies of acid phosphatases from pathogenic bacteria

Felts, Richard Levi, January 2007 (has links)
Thesis (Ph.D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 23, 2009) Vita. Includes bibliographical references.
7

Mécanismes moléculaires impliqués dans la virulence et la réponse au stress chez Francisella tularensis / Molecular mechanisms involved in the virulence and the answer to the stress at Francisella tularensis

Dieppedale, Jennifer 28 September 2012 (has links)
Francisella tularensis, agent étiologique de la tularémie, classée parmi les bactéries pathogènes les plus infectieuses pour l’homme, possède une palette d’enzymes lui permettant de faire face au stress oxydatif, notamment à l’intérieur des macrophages, sa principale cible cellulaire. Nous nous sommes consacrés à l’étude d’un nouveau locus potentiellement impliqué dans la réponse au stress oxydatif chez F. tularensis LVS : le locus FTL_0200-FTL_0209. L’analyse in silico de ce locus révèle une homologie de la partie proximale avec le locus batL impliqué dans l’aérotolérance chez Bacteroides fragilis. D'une part, le premier gène du locus, FTL_0200, détermine une protéine chaperon putative ATPase AAA+ de la famille MoxR. D'autre part, les gènes FTL_0201 à FTL_0205 présentent des motifs protéiques de type facteur von Willebrand de type A (VWA) et tétratricopeptide (TPR), potentiellement impliqués dans la liaison d’ions métalliques et les interactions protéineprotéine. Or, les gènes déterminant des ATPases AAA+ de type MoxR sont très souvent retrouvés dans des loci codant pour des prot ines à domaines VWA et TPR. Enfin, les données expérimentales disponibles sur ce type de loci suggèrent que les protéines chaperons MoxR s’associeraient avec des protéines à motifs VWA et TPR pour former des complexes impliqués dans l’insertion de cofacteurs métalliques sur leurs cibles dédiées (enzymes ou autres). Ces observations nous ont conduit à étudier le rôle du gène FTL_0200 dans la virulence de F. tularensis, et sa participation à la réponse au stress. L'étude du mutant de délétion LVS!FTL_0200 démontre que le gène FTL_0200 joue un rôle majeur dans la survie intramacrophagique, ainsi que dans la virulence de F. tularensis dans le modèle murin; elle confirme également sa participation à la résistance au stress. Une analyse transcriptionnelle du locus nous a permis d’identifier le site d’initiation de sa transcription ; les régions -10 et -35 correspondent à un site de fixation pour le facteur alternatif "32, intervenant en conditions de stress. Des expériences d’étiquetage moléculaire (TAPtag) sur les protéines FTL_0200, FTL_0201 et FTL_0205 codées par le locus, ont été réalisées afin d’identifier leurs partenaires d’interaction, et démontrer l’association des protéines produites par le locus en un complexe multimérique. L’analyse des résultats obtenus par spectrométrie de masse montre une interaction de FTL_0200 avec FTL_0201, une interaction de FTL_0201 avec FTL_0205 et une interaction de FTL_0205 avec FTL_0207, suggérant l’association de ces protéines en un complexe multimérique. De plus, les trois protéines, plus particulièrement FTL_0205, semblent interagir avec des enzymes proches ou internes au cycle de Krebs : l’-cétoglutarate déshydrogénase (KGDH), la pyruvate déshydrogénase (PDH) et l’acétyl-CoA carboxylase (ACC). Une expérience de double hybride bactérien confirme partiellement ces résultats. La protéine FTL_0205, présentant beaucoup plus d’interactions que les deux autres protéines, le gène correspondant a été muté. Il présente une sensibilité très accrue au stress oxydatif ainsi qu’un défaut de multiplication dans la lignée de macrophages murins primaires issus de moelle osseuse, et une atténuation de virulence dans les souris. L’activité des trois enzymes métaboliques découvertes dans les expériences de TAP, a été mesurée chez les mutants FTL_0200 et FTL_0205, et comparée à celle de la souche sauvage. La KGDH et la PDH présentent une activité significativement diminuée chez les deux mutants, tandis que l’activité de l’ACC reste inchangée. Les enzymes du cycle de Krebs participent à la synthèse de certains acides aminés. Une expérience d’infection cellulaire, avec ajout de casaminoacides, chez le mutant FTL_0205 montre une restauration de sa virulence au niveau de celle de la souche sauvage. / Pas de résumé en anglais
8

Francisella tularensis infection induces macrophage cell death /

Lai, Xin-He, January 2004 (has links)
Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.
9

Mechanisms and consequences of neutrophil apoptosis inhibition by Francisella tularensis

McCracken, Jenna Mae 01 May 2017 (has links)
Francisella tularensis is the causative agent of the life-threatening disease tularemia. The Centers for Disease Control considers F. tularensis among the most likely agents of biowarfare due to its high mortality rate, ease of aerosol transmission, and low infectious dose. A fundamental aspect of tularemia pathogenesis is the overwhelming accumulation of neutrophils in the lung that are incapable of bacterial clearance and furthermore injurious to the host tissue, as neutrophilia exacerbates disease and blockade of neutrophil influx into the lungs favors host survival. We hypothesized that the pathologic accretion of neutrophils may be the result of decreased neutrophil death and/or decreased clearance by macrophages. Our lab recently demonstrated that F. tularensis delays neutrophil apoptosis by at least 48 hours to preserve its replicative niche, but the mechanism by which this occurs was poorly defined. Here, we investigate alterations in neutrophil apoptosis and survival signaling at the molecular level and find that, in addition to effects on neutrophil transcription, F. tularensis also modulates protein abundance, activity, and subcellular localization. Specifically, we report that F. tularensis preserves mitochondrial integrity by inhibiting the pro-apoptotic proteins Bid and Bax as well as maintaining expression of the pro-survival factors XIAP and calpastatin. Moreover, we found that infection diminishes the ability of R-roscovitine to induce apoptosis, suggesting bacterial modulation of CDK-mediated survival signaling. Following apoptosis, effete neutrophils are rapidly cleared by macrophages in a process termed efferocytosis to avoid neutrophil progression to secondary necrosis and consequent host tissue damage. We demonstrate for the first time that neutrophils laden with F. tularensis are readily consumed by macrophages and release their infectious cargo into the macrophage cytoplasm. The engulfing cell is unable to eradicate the infection and extensive bacterial replication ensues. Intriguingly, we found that unlike other pathogens, covert infection of macrophages by F. tularensis triggers an inflammatory cytokine response that is highly similar to that of directly infected cells, suggesting that efferocytosis is not an essential virulence mechanism for this bacterium. Together, these studies significantly advance our understanding of fundamental F. tularensis virulence mechanisms and disease pathophysiology as well as shed light on other inflammatory disorders characterized by dysregulated neutrophil turnover and clearance.
10

A matter of life or death: modulation of neutrophil apoptosis and complement activation by Francisella tularensis

Schwartz, Justin Todd 01 May 2013 (has links)
Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia, a severe and potentially fatal disease in humans. This pathogen is extremely infectious by the aerosol route and inhalation of as few as 10 organisms can cause severe pneumonic disease. Consequently, F. tularensis was developed as a bioweapon by several nations and is considered a category A select agent by the Centers for Disease Control and Prevention. The ability of F. tularensis to cause overwhelming infections at low infectious doses suggests this organism has adapted efficient mechanisms to evade containment by the host innate immune system. The goal of this thesis was to better understand the mechanisms by which Francisella modulates innate host defenses, with particular focus on interactions between this pathogen and two important effectors of innate immunity: neutrophils and the complement system. We demonstrate that F. tularensis profoundly modulates neutrophil lifespan during infection, delaying spontaneous apoptosis by inhibiting both the intrinsic and extrinsic apoptotic pathways to maintain an intracellular niche for persistence and proliferation. Furthermore, we show that F. tularensis can override activation of the apoptotic program induced by extracellular apoptotic signals that may drive neutrophil apoptosis at the site of infection. Initial characterization of the molecular mechanisms behind apoptosis inhibition by this pathogen suggests that F. tularensis employs multiple, redundant mechanisms to promote global anti-apoptosis in the cell. Transcriptome analyses of infected PMNs using oligonucleotide microarrays show that 365 unique apoptosis and cell survival genes are differentially regulated between 3-24 hr, several of which directly modulate intrinsic and extrinsic pathway signaling. Moreover, we demonstrate that levels of the potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), are maintained over the course of infection, which may represent an important mechanism of caspase inhibition by this pathogen. We also confirm reports that F. tularensis can activate complement during incubation in nonimmune serum, and demonstrate for the first time that natural IgM antibodies bind to the bacterial surface and mediate complement opsonization to promote phagocytosis by both human neutrophils and macrophages. Finally, we identify the first neutrophil receptors, CR1 and CR3, involved in the uptake of complement-opsonized F. tularensis. In sum, our data presented here significantly advance our understanding of the host-pathogen relationship between F. tularensis and components of innate immunity, and suggest that this pathogen modulates both neutrophil and complement function to evade innate immune defenses and cause disease.

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