Affiliation:
1. Division of Infectious Diseases, LAC-Harbor UCLA Medical Center, Torrance, California 90509
2. David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90024
Abstract
ABSTRACT
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
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 of
ssd1
Δ/
ssd1
Δ 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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
37 articles.
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