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Eukaryotic Cell, October 2009, p. 1498-1510, Vol. 8, No. 10
1535-9778/09/$08.00+0     doi:10.1128/EC.00165-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells ^,

Hyunsook Park,¹ Yaoping Liu,¹ Norma Solis,¹ Joshua Spotkov,¹ Jessica Hamaker,² Jill R. Blankenship,^2, Michael R. Yeaman,^1,3 Aaron P. Mitchell,^4, Haoping Liu,⁴ and Scott G. Filler^1,3*

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California,¹ Columbia University, New York, New York,² David Geffen School of Medicine at UCLA, Los Angeles, California,³ Department of Biological Chemistry, College of Medicine, University of California—Irvine, Irvine, California⁴

Received 11 June 2009/ Accepted 10 August 2009

Candida albicans interacts with oral epithelial cells during oropharyngeal candidiasis and with vascular endothelial cells when it disseminates hematogenously. We set out to identify C. albicans genes that govern interactions with these host cells in vitro. The transcriptional response of C. albicans to the FaDu oral epithelial cell line and primary endothelial cells was determined by microarray analysis. Contact with epithelial cells caused a decrease in transcript levels of genes related to protein synthesis and adhesion, whereas contact with endothelial cells did not significantly influence any specific functional category of genes. Many genes whose transcripts were increased in response to either host cell had not been previously characterized. We constructed mutants with homozygous insertions in 22 of these uncharacterized genes to investigate their function during host-pathogen interaction. By this approach, we found that YCK2, VPS51, and UEC1 are required for C. albicans to cause normal damage to epithelial cells and resist antimicrobial peptides. YCK2 is also necessary for maintenance of cell polarity. VPS51 is necessary for normal vacuole formation, resistance to multiple stressors, and induction of maximal endothelial cell damage. UEC1 encodes a unique protein that is required for resistance to cell membrane stress. Therefore, some C. albicans genes whose transcripts are increased upon contact with epithelial or endothelial cells are required for the organism to damage these cells and withstand the stresses that it likely encounters during growth in the oropharynx and bloodstream.

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* Corresponding author. Mailing address: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson St., Torrance, CA 90502. Phone: (310) 222-3813. Fax: (310) 782-2016. E-mail: sfiller{at}ucla.edu

Published ahead of print on 21 August 2009.

Supplemental material for this article may be found at http://ec.asm.org/.

Present address: Department of Microbiology, Carnegie Mellon University, Pittsburgh, PA 15213.

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Eukaryotic Cell, October 2009, p. 1498-1510, Vol. 8, No. 10
1535-9778/09/$08.00+0     doi:10.1128/EC.00165-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.