Affiliation:
1. Institute of Life Science and School of Medicine, Swansea University, Swansea SA2 8PP, Wales, United Kingdom
2. University Medical Center Göttingen, Institute for Medical Microbiology and German National Reference Center for Systemic Mycoses, Göttingen, Germany
Abstract
ABSTRACT
A clinical isolate of
Candida albicans
was identified as an
erg5
(encoding sterol C22 desaturase) mutant in which ergosterol was not detectable and ergosta 5,7-dienol comprised >80% of the total sterol fraction. The mutant isolate (CA108) was resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole (MIC values, 64, 8, 2, 1, and 2 μg ml
−1
, respectively); azole resistance could not be fully explained by the activity of multidrug resistance pumps. When susceptibility tests were performed in the presence of a multidrug efflux inhibitor (tacrolimus; FK506), CA108 remained resistant to azole concentrations higher than suggested clinical breakpoints for
C. albicans
(efflux-inhibited MIC values, 16 and 4 μg ml
−1
for fluconazole and voriconazole, respectively). Gene sequencing revealed that CA108 was an
erg11 erg5
double mutant harboring a single amino acid substitution (A114S) in sterol 14α-demethylase (Erg11p) and sequence repetition (10 duplicated amino acids), which nullified C22 desaturase (Erg5p) function. Owing to a lack of ergosterol, CA108 was also resistant to amphotericin B (MIC, 2 μg ml
−1
). This constitutes the first report of a
C. albicans erg5
mutant isolated from the clinic.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
129 articles.
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