Proteomic profiling of yeast - and hyphal-specific responses of Candida albicans to the antifungal agent, HWY-289

Ki Young Kim, Yu Kyong Shin, Kap Chul Kang, Jong Shin Yoo, Jung Ho Kim, Young-Ki Paik

Research output: Contribution to journalArticle

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Abstract

Virulence of Candida albicans is attributable to its unique dimorphic transition from non-pathogenic yeast cells to pathogenic hyphal cells. We previously discovered a novel antifungal agent, known as HWY-289. To characterize the mechanism underlying HWY-289 antifungal activity, we performed 2-DE to identify proteins that were differentially expressed during yeast-to-hyphal transition and in response to HWY-289. Twenty-four differentially expressed protein spots were identified in HWY-289-treated yeast. Most differentially expressed proteins were involved in carbohydrate-derived energy metabolism, cellular detoxification, and antioxidant defenses. Two proteins were involved in cell cycle regulation and DNA processing, and both were downregulated by HWY-289, suggesting that this agent might promote cell death by weakening cellular defense systems. HWY-289 inhibited yeast-to-hyphal transition in a dose-dependent manner. 2-DE analysis of hyphae uncovered several proteins that were induced during yeast-to-hyphal transition. Of these, aconitase and phosphatidylinositol transfer protein were down-regulated by HWY-289, suggesting that they mediate the antifungal effects of HWY-289. Finally, RT-PCR analysis revealed that HWY-289 induced expression of three RAS-related genes (CcCST20, CaHST7, and CaCPH1) in yeast cells, but suppressed their expression in hyphae. Thus, the antifungal action of HWY-289 may be attributable to its ability to disrupt prohyphal RAS signaling.

Original languageEnglish
Pages (from-to)452-461
Number of pages10
JournalProteomics - Clinical Applications
Volume3
Issue number4
DOIs
Publication statusPublished - 2009 May 14

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Candida
Antifungal Agents
Candida albicans
Proteomics
Yeast
Yeasts
Hyphae
Cells
Proteins
HWY289
Phospholipid Transfer Proteins
Aconitate Hydratase
Detoxification
Cell death
Energy Metabolism
Virulence
Cell Cycle
Cell Death
Down-Regulation
Antioxidants

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry

Cite this

Kim, Ki Young ; Shin, Yu Kyong ; Kang, Kap Chul ; Yoo, Jong Shin ; Kim, Jung Ho ; Paik, Young-Ki. / Proteomic profiling of yeast - and hyphal-specific responses of Candida albicans to the antifungal agent, HWY-289. In: Proteomics - Clinical Applications. 2009 ; Vol. 3, No. 4. pp. 452-461.
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Proteomic profiling of yeast - and hyphal-specific responses of Candida albicans to the antifungal agent, HWY-289. / Kim, Ki Young; Shin, Yu Kyong; Kang, Kap Chul; Yoo, Jong Shin; Kim, Jung Ho; Paik, Young-Ki.

In: Proteomics - Clinical Applications, Vol. 3, No. 4, 14.05.2009, p. 452-461.

Research output: Contribution to journalArticle

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