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Small molecule modulation of morphology and metabolism in Candida albicans / by Allia Kaye Smith

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Author	Smith, Allia Kaye.
Title	Small molecule modulation of morphology and metabolism in Candida albicans / by Allia Kaye Smith
Date	2014
Abstract	Candida albicans is a fungal species that naturally exists as a commensal member of the human microbiota, but can assume a pathogenic lifestyle and subsequently induce life-threatening systemic infections. The ability of the fungus to grow in different morphologies--yeast or filamentous forms--has been recognized as a virulence trait of this opportunistic pathogen. This thesis work primarily aimed to increase understanding of how the switch between growth in these two morphologies is regulated by endogenous and exogenous small molecules. First, I focused on the regulation of morphology by the C. albicans produced quorum sensing molecule farnesol. These studies, which relied heavily on microscopic techniques, were the first to show the stimulatory effect of farnesol on the filament-to-yeast transition and that the pathway required for the induction of filamentation is also required to maintain growth in this morphology. Next, I focused on the effect of endogenous small molecules on morphological transitions. Specifically, I studied the effects of redox-active pyocyanin which is secreted by the gram-negative bacteria Pseudomonas aeruginosa, which is commonly co-isolated with C. albicans from, for example, the cystic fibrosis lung as well as biofilms formed on implanted biomedical devices such as catheters. These studies, which relied on techniques such as genetic screens, metabolomics analyses and biochemical assays, provided a mechanistic link between fungal morphology and metabolism, and indicated metabolism has to be decreased below a certain threshold in order to influence morphology. Overall, the results of this thesis provide further mechanistic insight on how endogenous and exogenous small molecules influence the morphology of C. albicans.
Description	xx, 217 leaves : ill.
Format	application/pdf
College	Dartmouth Medical School. Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1277

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