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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette
Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette
Theses and Dissertations (ETD)
Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
Theses and Dissertations (ETD)
"Candida albicans is a commensal organism commonly colonizing the human gut and skin. As an opportunistic pathogen, it can cause persistent and serious infections in individuals with compromised immune systems, including the very young and elderly. Moreover, C. albicans can cause a wide spectrum of diseases ranging from superficial mucosal infections to life-threatening invasions of the organs and bloodstream. Candida species are the most common cause of invasive fungal disease, which is associated with high mortality and imposes a heavy toll on the healthcare system. Over the last 30 years, the azole antifungals have been a mainstay of antifungal therapy, …
Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley
Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley
Theses and Dissertations (ETD)
Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …
Endosomal Trafficking As A Determinant Of Antifungal Tolerance In The Pathogenic Fungus Candida Albicans, Arturo Luis Luna
Endosomal Trafficking As A Determinant Of Antifungal Tolerance In The Pathogenic Fungus Candida Albicans, Arturo Luis Luna
Theses and Dissertations (ETD)
Several important antifungal drugs inhibit the synthesis of ergosterol, a lipid that modulates the thickness, fluidity and permeability of fungal cell membranes. These include the azole antifungals, which block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of ‘toxic’ sterol intermediates are both thought to cause plasma membrane dysfunction and ultimately growth arrest. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole, …
Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek
Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek
Theses and Dissertations (ETD)
Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …