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Note: Thesis (Ph.D. -- Brown University (2015)
Name: Personal
Name: Personal
Name: Personal
Name: Personal
Name: Personal
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Abstract: Fungal pathogens utilize a variety of strategies to adapt to environmental cues and to thrive in different host niches. This includes phenotypic switching, in which cells undergo heritable transitions between alternative phenotypic states. Such transitions are critical to the biology of Candida species, which are the most common human fungal pathogens, and can grow as benign commensals but have the potential to become opportunistic pathogens, particularly targeting immunocompromised hosts. Despite the importance of phenotypic transitions, there remains a limited understanding of the mechanisms underlying these transitions or how they evolved. Recent studies of phenotypic switching have revealed that complex transcriptional networks regulate switching. Investigation of these regulatory networks, including the rewiring of networks between species, can provide new insights into how such networks evolve as well as their contributions to organismal fitness. The work described here identifies a novel “white-opaque” phenotypic switch in Candida tropicalis, an opportunistic fungal pathogen in the Candida clade. This phenotypic switch is limited to three related Candida species, although its regulation is mediated by conserved transcription factors. The discovery of the C. tropicalis white-opaque switch is presented in Chapter 2, including the properties of the phenotypic states, the related gene expression profiles, and the regulation of sexual mating by the switch. In Chapter 3, the role of the Wor1 transcription factor in regulating opaque cell formation is presented, as well as the role of this factor in filamentation and biofilm formation in C. tropicalis. In Chapter 4, a third phenotypic state, termed the intermediate state, is identified, which further distinguishes the C. tropicalis switch from that in other Candida species. Finally, this work shows that ectopic WOR1 expression causes unstable induction of the opaque state in C. tropicalis, illustrating another significant difference from the related switch in C. albicans. Comparison of the features identified in our studies with that of the features of the C. albicans white-opaque switch has revealed divergence both in upstream effectors of the switch as well as downstream outcomes. Overall, this work shows that an epigenetic switch that looks phenotypically similar can have widely different outcomes in the context of different species.
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Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/845623")
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Identifier: DOI: 10.7301/Z0K35S17
Access Condition: rights statement (href="http://rightsstatements.org/vocab/InC/1.0/"): In Copyright
Access Condition: restriction on access: Collection is open for research.
Type of Resource (primo): dissertations