Eukaryotic Cell
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Eukaryotic Cell doi:10.1128/EC.00340-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans

Silvia Argimón, Jill A. Wishart, Roger Leng, Susan Macaskill, Abigail Mavor, Thomas Alexandris, Susan Nicholls, Andrew W. Knight, Brice Enjalbert, Richard Walmsley, Frank C. Odds, Neil A.R. Gow, and Alistair J. P. Brown*

School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK; Gentronix Limited, CTF Building, 46 Grafton Street, Manchester, M13 9NT. UK

* To whom correspondence should be addressed. Email: al.brown{at}abdn.ac.uk.


   Abstract

Candida albicans expresses specific virulence traits that promote disease establishment and progression. These include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion, and cell surface adhesins that promote attachment to the host. Here we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, whilst the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between -471 and -321 of the promoter. Further 5' or 3' deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1 and Bcr1 are essential for the transcriptional activation of ALS3, Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signalling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen.




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