Proteomic profiling of yeast- and hyphal-specific responses of Candida albicans to the antifungal agent, HWY-289.
Virulence of Candida albicans is attributable to its unique dimorphic transition from nonpathogenic 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 downregulated 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.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Sudaemoon-ku, Seoul, Korea; Current address: Department of Biochemistry and Molecular Biology, Johns Hopkins University, 615 N. Wolfe Street, Room W8118, Baltimore, MD 21205, USA.
Ki-Young
KY
Kim
Yu-Kyong
YK
Shin
Kap-Chul
KC
Kang
Jong-Shin
JS
Yoo
Jung-Ho
JH
Kim
Young-Ki
YK
Paik