Open AccessSSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans
Author(s) -
Kimberly D. Gank,
Michael R. Yeaman,
Satoshi Kojima,
Nannette Y. Yount,
HyunSook Park,
John E. Edwards,
Scott G. Filler,
Yue Fu
Publication year - 2008
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.00402-07
Subject(s) - candida albicans , biology , antimicrobial peptides , virulence , corpus albicans , microbiology and biotechnology , mutant , peptide , gene , phenotype , beta defensin , genetics , antimicrobial , biochemistry
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 ofC. albicans , 36082R , is hypervirulent in animal models versus its susceptible counterpart (36082S ). The current study aimed to identify a genetic basis for antimicrobial peptide resistance inC. albicans . Screening of aC. albicans genomic library identifiedSSD1 as capable of conferring peptide resistance to a susceptible surrogate,Saccharomyces cerevisiae . Sequencing confirmed that the predicted translation products of 36082S and 36082R SSD1 genes were identical. However, Northern analyses corroborated thatSSD1 is expressed at higher levels in 36082R than in 36082S . In isogenic backgrounds,ssd1 Δ/ssd1 Δ null mutants were significantly more susceptible to antimicrobial peptides than parental strains but had equivalent susceptibilities to nonpeptide stressors. Moreover,SSD1 complementation ofssd1 Δ/ssd1 Δ mutants restored parental antimicrobial peptide resistance phenotypes, and overexpression ofSSD1 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 thatSSD1 is integral toC. albicans resistance to host defense peptides, a phenotype that appears to enhance the virulence of this organism in vivo.