Expanding the Candida albicans response to acidic pH
Abstract
The aim of the studies presented in this dissertation is to further our knowledge on the pathways responsible for responding to the effects of external pH in Candida albicans. For the majority of this work, we focused on identifying novel genetic pathways responsible for acidic pH repression of the initiation of hyphal morphogenesis, and provided some preliminary studies on pH effects on the C. albicans cell wall.
Chapter 1 presents an introductory overview on the current knowledge of hyphal growth, and how it is regulated by a variety of environmental conditions encountered by the fungus.
In Chapter 2, we showed that translation is important for effective hyphal growth, and inhibition of translation genetically or chemically delays hyphal initiation.
The study in Chapter 3 identified several genes that are responsible for acidic pH repression of hyphal initiation. We focused on the Hog1 stress response pathway and identified Hog1 activity as a requirement for suppressing hyphal initiation in acidic pH and in the presence of stress. We observed that acidic pH (~4) regulates Hog1 by stabilizing Hog1 phosphorylation, different from stress stimulation of Hog1, by suppressing the expression of the tyrosine phosphatase ptp3. Furthermore, stresses that activate Hog1 also reveal an impaired ability to initiate hyphal growth, supporting the role of Hog1 in repressing hyphal initiation. This study also identified Sfl1 as a key hyphal repressor that functions down-stream of the Hog1 pathway. The Hog1-Sfl1 pathway is activated in response to stress parallel to the Nrg1 repressor. Overall, we have identified a new genetic interaction and regulation that’s necessary for hyphal regulation.
In Chapter 4, we present preliminary data showing that β-Glucans are exposed in acidic pH but live cells are able to protect themselves from that exposure. We have experimental results that exclude the Hog1 and the Cek1MAPK pathways in mediating this protection. Therefore, we propose a genetic screen to identify mutants that are defective in their protection of β-Glucans