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Applied and Environmental Microbiology, June 2009, p. 3663-3672, Vol. 75, No. 11
0099-2240/09/$08.00+0     doi:10.1128/AEM.00098-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Hypoxic Adaptation by Efg1 Regulates Biofilm Formation by Candida albicans{triangledown}

Catrin Stichternoth and Joachim F. Ernst*

Institut für Mikrobiologie, Molekulare Mykologie, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany

Received 15 January 2009/ Accepted 24 March 2009

Hypoxia is encountered frequently by Candida albicans during systemic infection of the human host. We tested if hypoxia allows biofilm formation by C. albicans, which is a major cause of perseverance and antifungal resistance in C. albicans infections. Using an in vitro biofilm system, we unexpectedly discovered that several positive regulators of biofilm formation during normoxia, including Tec1, Ace2, Czf1, Och1, and Als3, had little or no influence on biofilm development during hypoxia, irrespective of the carbon dioxide level, indicating that C. albicans biofilm pathways differ depending on the oxygen level. In contrast, the Efg1 and Flo8 regulators were required for both normoxic and hypoxic biofilm formation. To explore the role of Efg1 during hypoxic and/or biofilm growth, we determined transcriptome kinetics following release of EFG1 expression by a system under transcriptional control of a doxycycline-inducible promoter. During hypoxia, Efg1 rapidly induced expression of all major classes of genes known to be associated with normoxic biofilm formation, including genes involved in glycolysis, sulfur metabolism, and antioxidative and peroxisome activities, as well as genes for iron uptake. The results suggest that hypoxic adaptation mediated by the Efg1 and Flo8 regulators is required even during normoxic biofilm development, while hypoxic biofilm formation in deep tissues or in organs may generate foci of C. albicans infections.

* Corresponding author. Mailing address: Institut für Mikrobiologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1/Geb. 26.12, D-40225 Düsseldorf, Germany. Phone and fax: 49 (211) 811-5176. E-mail: joachim.ernst{at}uni-duesseldorf.de

{triangledown} Published ahead of print on 3 April 2009.

Applied and Environmental Microbiology, June 2009, p. 3663-3672, Vol. 75, No. 11
0099-2240/09/$08.00+0     doi:10.1128/AEM.00098-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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