Waikialoid A Suppresses Hyphal Morphogenesis and Inhibits Biofilm Development in Pathogenic Candida albicans

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• 作者：Xiaoru Wang ; Jianlan You ; Jarrod B. King ; Douglas R. Powell ; Robert H. Cichewicz
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：April 27, 2012
• 年：2012
• 卷：75
• 期：4
• 页码：707-715
• 全文大小：417K
• 年卷期：v.75,no.4(April 27, 2012)
• ISSN：1520-6025

文摘

A chemically prolific strain of Aspergillus was isolated from a soil sample collected near Waikiki Beach, Honolulu, Hawaii. The fungus produced several secondary metabolites, which were purified and placed in our natural products library and were later screened for substances capable of inhibiting biofilm formation by Candida albicans. It was determined that one of the secondary metabolites from the Hawaiian fungal isolate, a new complex prenylated indole alkaloid named waikialoid A (1), inhibited biofilm formation with an IC₅₀ value of 1.4 渭M. Another structurally unrelated, presumably polyketide metabolite, waikialide A (15), also inhibited C. albicans biofilm formation, but was much less potent (IC₅₀ value of 32.4 渭M). Microscopy studies revealed that compound 1 also inhibited C. albicans hyphal morphogenesis. While metabolite 1 appears ineffective at disrupting preformed biofilms, the accumulated data indicate that the new compound may exert its activity against C. albicans during the early stages of surface colonization involving cell adherence, hyphal development, and/or biofilm assembly. Unlike some other stephacidin/notoamide compounds, metabolite 1 was not cytotoxic to fungi or human cells (up to 200 渭M), which makes this an intriguing model compound for studying the adjunctive use of biofilm inhibitors in combination with standard antifungal antibiotics.