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Eukaryotic Cell, August 2008, p. 1318-1327, Vol. 7, No. 8
1535-9778/08/$08.00+0     doi:10.1128/EC.00402-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

SSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans

Kimberly D. Gank,¹ Michael R. Yeaman,^1,2,* Satoshi Kojima,¹ Nannette Y. Yount,¹ Hyunsook Park,¹ John E. Edwards Jr.,^1,2 Scott G. Filler,^1,2 and Yue Fu^1,2,

Division of Infectious Diseases, LAC-Harbor UCLA Medical Center, Torrance, California 90509,¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90024²

Received 31 October 2007/ Accepted 15 May 2008

Candida albicans is usually a harmless human commensal. Because inflammatory responses are not normally induced by colonization, antimicrobial peptides are likely integral to first-line host defense against invasive candidiasis. Thus, C. albicans must have mechanisms to tolerate or circumvent molecular effectors of innate immunity and thereby colonize human tissues. Prior studies demonstrated that an antimicrobial peptide-resistant strain of C. albicans, 36082^R, is hypervirulent in animal models versus its susceptible counterpart (36082^S). The current study aimed to identify a genetic basis for antimicrobial peptide resistance in C. albicans. Screening of a C. albicans genomic library identified SSD1 as capable of conferring peptide resistance to a susceptible surrogate, Saccharomyces cerevisiae. Sequencing confirmed that the predicted translation products of 36082^S and 36082^R SSD1 genes were identical. However, Northern analyses corroborated that SSD1 is expressed at higher levels in 36082^R than in 36082^S. In isogenic backgrounds, ssd1/ssd1 null mutants were significantly more susceptible to antimicrobial peptides than parental strains but had equivalent susceptibilities to nonpeptide stressors. Moreover, SSD1 complementation of ssd1/ssd1 mutants restored parental antimicrobial peptide resistance phenotypes, and overexpression of SSD1 conferred enhanced peptide resistance. Consistent with these in vitro findings, ssd1 null mutants were significantly less virulent in a murine model of disseminated candidiasis than were their parental or complemented strains. Collectively, these results indicate that SSD1 is integral to C. albicans resistance to host defense peptides, a phenotype that appears to enhance the virulence of this organism in vivo.

Published ahead of print on 30 May 2008.

These authors contributed equally to this work.