Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence.

Proceedings of the National Academy of Sciences of the United States of America
Patricia L CarlisleDavid Kadosh

Abstract

Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments (elongated cells attached end-to-end). Because typical C. albicans infections contain a mixture of these morphologies it has, for many years, been difficult to assess the relative contribution of each form to virulence. In addition, the regulatory mechanisms that determine growth in pseudohyphal and hyphal morphologies are largely unknown. To address these questions we have generated a C. albicans strain that can be genetically manipulated to grow completely in the hyphal form under non-filament-inducing conditions in vitro. This was achieved by inducing high-level constitutive expression of UME6, a recently identified filament-specific transcriptional regulator of C. albicans hyphal extension. We show that high-level UME6 expression significantly increases hyphal formation and promotes virulence in a mouse model of systemic candidiasis. Our results strongly suggest that shifting the morphology of a C. albicans population toward the hyphal form, and/or increasing hyphal-specific gene expression, during the course of infection is sufficient to improve virulence potential....Continue Reading

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Citations

Jan 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Robert J Bastidas, Joseph Heitman
Dec 18, 2012·Molecular Biology of the Cell·Patricia L Carlisle, David Kadosh
Mar 3, 2010·Antimicrobial Agents and Chemotherapy·Govindsamy VediyappanChristophe d'Enfert
Apr 23, 2013·Applied and Environmental Microbiology·Mélanie GerphagnonTélesphore Sime-Ngando
Jul 27, 2010·Eukaryotic Cell·Ian A ClearyStephen P Saville
Jul 21, 2009·Eukaryotic Cell·Jeffrey Sabina, Victoria Brown
May 28, 2013·Eukaryotic Cell·Douglas A JohnstonGlen E Palmer
Jul 19, 2011·Eukaryotic Cell·Delma S ThompsonDavid Kadosh
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