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Stress Response Pathways Regulate Dr...

Xie, Jing Lin.

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Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans./
Author:	Xie, Jing Lin.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	181 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.
Contained By:	Dissertation Abstracts International78-10B(E).
Subject:	Molecular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10239784
ISBN:	9781369854787

Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans.
Xie, Jing Lin.

Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 181 p.

Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2017.

The dimorphic yeast Candida albicans is a leading causative agent of fungal infections in humans. Critical to C. albicans pathogenesis is its ability to transition between yeast and filamentous forms. Currently, a major clinical problem is the frequent emergence of resistance to existing antifungal drugs. Development of new antifungal agents remains a difficult process, partly due to the conservation of many potential therapeutic targets between C. albicans and humans. Moreover, stress responses in C. albicans enhance antifungal tolerance and enable drug resistance. Therefore, tactical targeting of specific stress response pathways that regulate drug resistance and morphogenesis in combination with known antifungal agents may provide a viable strategy to enhance the efficacy of antifungals and suppress the emergence of antifungal drug resistance. My doctoral research focuses on two cellular stress response pathways that are essential for drug resistance and the morphological transition in C. albicans. First, I uncover the regulatory circuitry through which the transcription factor Cas5 mediates cell wall stress responses, and establish Cas5 as a novel regulator of resistance to the echinocandin caspofungin. This represents the first example of transcriptional regulation as a mechanism of echinocandin resistance. Second, I reveal a novel and essential role for the protein kinase Pkc1 in regulating morphogenesis of C. albicans. I demonstrate that Pkc1 functions downstream of Rho1 in a signaling pathway that operates in parallel with the Ras1-PKA pathway. This is only the second pathway identified in C. albicans that has the capacity to integrate multiple filament-inducing cues and transduce the signals necessary for the transition from yeast to filamentous growth. Together, this research highlights the central role of cellular stress circuitry in drug resistance and morphogenesis, and uncovers attractive targets for the development of novel antifungal drugs, suggesting new avenues for combination therapies with current antifungal agents.

ISBN: 9781369854787Subjects--Topical Terms:

517296
Molecular biology.

Stress Response Pathways Regulate Drug Resistance and Morphogenesis in the Human Fungal Pathogen Candida albicans.
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