Affiliation:
1. Departments of Pharmacy
2. Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee 38103
3. Pharmaceutical Sciences
4. Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163
5. College of Pharmacy, and Departments of Pediatrics
Abstract
ABSTRACT
Antifungal agents exert their activity through a variety of mechanisms, some of which are poorly understood. We examined changes in the gene expression profile of
Candida albicans
following exposure to representatives of the four currently available classes of antifungal agents used in the treatment of systemic fungal infections. Ketoconazole exposure increased expression of genes involved in lipid, fatty acid, and sterol metabolism, including
NCP1
,
MCR1
,
CYB5
,
ERG2
,
ERG3
,
ERG10
,
ERG25
,
ERG251
, and that encoding the azole target,
ERG11
. Ketoconazole also increased expression of several genes associated with azole resistance, including
CDR1
,
CDR2
,
IFD4
,
DDR48
, and
RTA3
. Amphotericin B produced changes in the expression of genes involved in small-molecule transport (
ENA21
), and in cell stress (
YHB1
,
CTA1
,
AOX1
, and
SOD2
). Also observed was decreased expression of genes involved in ergosterol biosynthesis, including
ERG3
and
ERG11
. Caspofungin produced changes in expression of genes encoding cell wall maintenance proteins, including the β-1,3-glucan synthase subunit
GSL22
, as well as
PHR1
,
ECM21
,
ECM33
, and
FEN12
. Flucytosine increased the expression of proteins involved in purine and pyrimidine biosynthesis, including
YNK1
,
FUR1
, and that encoding its target,
CDC21
. Real-time reverse transcription-PCR was used to confirm microarray results. Genes responding similarly to two or more drugs were also identified. These data shed new light on the effects of these classes of antifungal agents on
C. albicans
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
286 articles.
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