Biomedical Sciences ETDs

Publication Date

7-1-2014

Abstract

Candida albicans is a human fungal commensal and an opportunistic pathogen. It is a polymorphic fungus that is able to invade host cells and disseminate through tissues. C. albicans also form biofilms on medical devices and mucosal surfaces, which aid in the development of drug resistance, tissue colonization and evasion of host immunity. Disseminated candidiasis is associated with high mortality rates, especially in immunocompromised hosts. Concern about resistance to current antifungal therapies has led to a push to develop novel, alternative treatments. In this study, we investigated the antifungal activities of two agents: PPE-DABCO, a poly(phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolyte (CPE), and EO-OPE-1 (DABCO), an oligo-phenylene ethynylene (OPE). Both compounds generate singlet oxygen upon UV-irradiation. The effect of both compounds against C. albicans was tested in the dark and with photoactivation using light of the appropriate wavelength for each agent. We demonstrated that both compounds showed enhanced antifungal activity when irradiated with UV-light, reducing the viability of yeast in suspension. Activation of PPE-DABCO with the 405nm confocal laser was also able to significantly reduce the viability of C. albicans yeast and hyphal cells. Furthermore, by limiting the time of exposure to the 405nm laser to 20 minutes, we were able to isolate the effects of photoactivation of PPE-DABCO from effects due to phototoxicity, by assessing the subsequent hyphal growth. Neither dark nor light treatment with either compound was able to prevent the biofilm formation of surviving cells. This study provides evidence that PPE-DABCO and EO-DABCO act as potent antifungal agents upon photoactivation, and photoactivation is necessary to achieve full antifungal efficacy to reduce the viability of yeast and hyphae and prevent morphological transitioning.

Keywords

"candida, biocidal, reactive oxygen species, antifungal"

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Advisor

Neumann, Aaron

First Committee Member (Chair)

Wilson, Bridget

Second Committee Member

Neumann, Aaron

Third Committee Member

Witten, David

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