Thesis (M.S.)--Oregon State University, 2002. / Typescript (photocopy). Includes bibliographical references. Also available on the World Wide Web.

Systemic candidiasis is most commonly studied in animal models, particularly the murine intravenous (IV) challenge model, where infection with a virulent Candida albicans strain leads to increasing fungal kidney burdens and increasing pro-inflammatory cytokines in the kidneys. Based upon the finding that early renal levels of the chemokine KC correlate with infection outcome, a new in vitro model, utilising the murine renal M-1 cortical collecting duct epithelial cell line, was developed to evaluate virulence of C. albicans isolates and mutants, in attempts to reduce the number of mice used in C. albicans virulence studies, addressing the 3Rs. The epithelial cells were shown to respond only to live fungal cells, unlike immune cells, responding more robustly to hyphae rather than to cells growing as yeasts. We also demonstrate that non-albicans Candida species, which are attenuated in the mouse IV challenge model, are unable to elicit chemokine responses from mouse kidney epithelial cells, despite increasing the inoculums used. Renal epithelial cell responses observed in the new model reflect early events in the mouse model, with chemokines KC and MIP-2 produced in response to virulent C. albicans strains or mutants. This chemokine production correlates with C. albicans damage to epithelial cells. Some involvement of TLR4 signalling was demonstrated as blocking of TLR4 signalling reduced epithelial KC production, and it was demonstrated that the renal epithelial cells respond strongly to more complex glycan molecules. Using this new in vitro model we have confirmed that renal epithelial cells are able to discriminate between virulent and attenuated strains of C. albicans, allowing this model to be used as an initial screen for altered virulence and for investigating how renal epithelial cells detect the presence of pathogenic fungi.

Typescript Includes bibliographical references

Thesis (Ph. D.)--Oregon State University, 2003. / Typescript (photocopy). Includes bibliographical references. Also available on the World Wide Web.

Thesis (M.Ag.Sc.)--University of Adelaide, Dept. of Plant Pathology, 1965. / Typescript. Includes bibliographical references.

Thesis (Ph.D.)--Murdoch University, 2004. / Thesis submitted to the Division of Science and Engineering. Includes bibliographical references (p. 199-210).

One of the major aims of this thesis was to identify novel regulators that drive C. albicans adaptation during growth under different nutrient and temperature conditions. The classical stress response cascades have been previously characterised under standardized, but physiologically irrelevant growth conditions (YPD at 30°C). In this study these pathways and other regulators were examined under more physiologically relevant inputs because metabolic plasticity and thermo-tolerance have been shown to affect stress adaptation (Arguelles et al., 1999; Brown et al., 2014; Cowen, 2009; Diezmann et al., 2014). In this study, we characterized 18.5% of the functional C. albicans ORFeome under 144 different stress conditions by employing a standardized system of robotic screening (Chapter 3). These screens highlighted extensive carbon and temperature-conditional regulators in C. albicans. We identified carbon-conditional contributions of the transcriptional regulators Sfp1 and Rtg3 to stress adaptation in this pathogenic fungus (Chapter 4). Sfp1 was found to regulate the expression of key stress regulators during growth on glucose, whereas Rtg3 induced the expression of these stress genes during growth on lactate. Our screens also revealed a distinct set of transcription factors, Hap43, Swi4, Sfp1, Cap1 and Zcf31, that control regulators of cell wall integrity and that promote antifungal drug resistance in a temperature dependent and yet Hsp90- independent manner. The screens also provided new information about a relatively obscure group of transcriptional regulators in C. albicans; the zinc cluster proteins with focus on Zcf3 and Zcf18 which we further pursued with RNA-sequencing to establish them as modulators of cell cycle, stress resistance and virulence in C. albicans. Lastly, our screens reveal a network of regulators that are homologous to human oncogenes and control fungal growth via modulation of TOR signaling. In conclusion, this thesis has revealed many novel targets for possible antifungal drug development and highlighted the extensive and intricate cross-talk between stress response modules facilitated by physiologically relevant nutrient sources and ambient temperatures.

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Biology." Includes bibliographical references (p. 25-27).

Thesis (M.S.)--Oregon State University, 1993. / Typescript (photocopy). Includes bibliographical references (leaves 132-140). Also available via the World Wide Web.

Thesis (M.S.)--Oregon State University, 1992. / Includes mounted photographs. Typescript (photocopy). Includes bibliographical references (leaves 35-39). Also available on the World Wide Web.