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Status |
Public on Mar 10, 2011 |
Title |
Conjugated linoleic acid inhibits hyphal growth in Candida albicans by modulating Ras1 cellular levels and down-regulating TEC1 expression |
Organism |
Candida albicans |
Experiment type |
Expression profiling by array
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Summary |
The polymorphic yeast Candida albicans exists in blastospore and filamentous forms. The switch from one morphological state to the other coincides with the expression of virulence factors, which makes the yeast-to-hypha transition an attractive target for the development of new antifungal agents. Because an untapped therapeutic potential resides in small molecules that hinder C. albicans filamentation, we characterized the inhibitory effect of conjugated linoleic acid (CLA) on hyphal growth and addressed its mechanism of action. CLA inhibited hyphal growth in a dose-dependent fashion, in both liquid- and solid-inducing media. The fatty acid blocked germ tube formation and impeded hyphal elongation. Global transcriptional profiling revealed that CLA downregulated the expression of hypha-specific genes and abrogated the induction of several morphogenesis regulators, including RAS1, TEC1 and UME6. CLA’s repressive effect on TEC1 expression was Ras1-dependent, but Efg1-independent. CLA treatment resulted in the delocalization of Ras1 and its degradation, resulting in the downregulation of the Ras1-cAMP-PKA signaling pathway. This study provides the biological and molecular explanations that underlie CLA’s ability to inhibit hyphal growth in C. albicans.
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Overall design |
Two-color experimental design that consistently used growth in Spider Media at 30℃ as the control. We tested the effect of high temperature as well as the effect of adding 100 mµ CLA at either low or high temperature. RNA from each replicate came from independent cultures.
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Contributor(s) |
Shareck J, Nantel A, Belhumeur P |
Citation(s) |
21357478 |
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Submission date |
Dec 02, 2010 |
Last update date |
Mar 22, 2012 |
Contact name |
Andre Nantel |
E-mail(s) |
andre.nantel@nrc-cnrc.gc.ca
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Phone |
514-496-6370
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Fax |
514-496-9127
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Organization name |
National Research Council of Canada
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Department |
Biotechnology Research Institute
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Street address |
6100 Royalmount
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City |
Montreal |
State/province |
QC |
ZIP/Postal code |
H4P 2R2 |
Country |
Canada |
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Platforms (1) |
GPL9818 |
NRC-BRI C. albicans expression microarray V2.0 |
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Samples (12)
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GSM634447 |
37℃ vs 30℃ rep4 |
GSM634448 |
Effect of Conjugated linoleic acid at 30℃ rep1 |
GSM634449 |
Effect of Conjugated linoleic acid at 30℃ rep2 |
GSM634450 |
Effect of Conjugated linoleic acid at 30℃ rep3 |
GSM634451 |
Effect of Conjugated linoleic acid at 30℃ rep4 |
GSM634452 |
Effect of Conjugated linoleic acid at 37℃ rep1 |
GSM634453 |
Effect of Conjugated linoleic acid at 37℃ rep2 |
GSM634454 |
Effect of Conjugated linoleic acid at 37℃ rep3 |
GSM634455 |
Effect of Conjugated linoleic acid at 37℃ rep4 |
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Relations |
BioProject |
PRJNA135635 |