Type
Text
Type
Dissertation
Advisor
van der Velden, Adrianus | Konopka, James B | Neiman, Aaron | Bliska, James.
Date
2015-05-01
Keywords
Adenylyl cyclase, cAMP, Candida albicans, hyphal growth, hyphal induction, pseudorevertants | Molecular biology
Department
Department of Molecular and Cellular Biology.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76480
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The human opportunistic fungal pathogen Candida albicans can undergo a transition from budding to hyphal growth in response to host cues that promotes tissue invasion and dissemination through the host. Accompanying the morphogenic change is an upregulation of genes that promote virulence. Morphogenic switching and subsequent gene regulation are required for full virulence in the host and are an area of intense study. It has been shown that increased production of cAMP by Cyr1 Adenylyl cyclase can induce hyphal growth. Further, it was proposed that activation of Cyr1 and an increase in cAMP were necessary for all hyphal growth in C. albicans. The main evidence for this necessity is that cells lacking Adenylyl cyclase (cyr1Δ) fail to induce hyphal growth in response to most physiological inducers. This evidence is not conclusive as deletion of CYR1 severely affects cellular health. I have demonstrated that signaling through Cyr1 and cAMP are not required for hyphal morphogenesis or virulence gene induction. I propose that cAMP-independent pathways are responsible for much of the morphogenic and gene regulatory signals produced by physiological inducers. My findings shed light on hyphal signaling in Candida albicans and will aid in the identification of drug targets and the development of novel therapeutics. | The human opportunistic fungal pathogen Candida albicans can undergo a transition from budding to hyphal growth in response to host cues that promotes tissue invasion and dissemination through the host. Accompanying the morphogenic change is an upregulation of genes that promote virulence. Morphogenic switching and subsequent gene regulation are required for full virulence in the host and are an area of intense study. It has been shown that increased production of cAMP by Cyr1 Adenylyl cyclase can induce hyphal growth. Further, it was proposed that activation of Cyr1 and an increase in cAMP were necessary for all hyphal growth in C. albicans. The main evidence for this necessity is that cells lacking Adenylyl cyclase (cyr1Δ) fail to induce hyphal growth in response to most physiological inducers. This evidence is not conclusive as deletion of CYR1 severely affects cellular health. I have demonstrated that signaling through Cyr1 and cAMP are not required for hyphal morphogenesis or virulence gene induction. I propose that cAMP-independent pathways are responsible for much of the morphogenic and gene regulatory signals produced by physiological inducers. My findings shed light on hyphal signaling in Candida albicans and will aid in the identification of drug targets and the development of novel therapeutics. | 80 pages
Recommended Citation
Parrino, Salvatore Michael, "Candida albicans Adenylyl cyclase – cAMP Pathway and Hyphal Growth | Candida albicans Adenylyl cyclase – cAMP Pathway and Hyphal Growth" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2395.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2395