Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans.
Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans.
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DOI：
10.1021/np2009994
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发表时间：
2012-04-27
影响因子：
5.1
通讯作者：
Cichewicz RH
中科院分区：
文献类型：
--
作者：
Wang X;You J;King JB;Powell DR;Cichewicz RH
从夏威夷檀香山威基基海滩附近采集的土壤样品中分离出一种化学多产的曲霉属菌株。该真菌产生了几种次级代谢产物，将其纯化并置于我们的天然产物库中，随后筛选能够抑制白色念珠菌生物膜形成的物质。经测定，夏威夷真菌分离株的一种次级代谢产物，一种名为waikialoid A（1）的新型复合异戊二烯化吲哚生物碱，可抑制生物膜形成，IC 50值为1.4 μM。另一种结构上不相关的聚酮代谢物waikialide A（15）也能抑制C。白色念珠菌生物膜形成，但效力低得多（IC 50值为32.4 μM）。显微镜研究表明，化合物1也抑制C。白色念珠菌菌丝形态发生。虽然代谢物1在破坏预先形成的生物膜方面似乎无效，但累积的数据表明新化合物可能对C.在涉及细胞粘附、菌丝发育和/或生物膜组装的表面定殖的早期阶段，与其他一些千金藤素/notoamide化合物不同，代谢物1对真菌或人类细胞没有细胞毒性（高达200 μM），这使得其成为研究生物膜抑制剂与标准抗真菌抗生素联合使用的有趣模型化合物。
A chemically prolific strain of Aspergillus was isolated from a soil sample collected near Waikiki Beach, Honolulu, Hawaii. The fungus produced several secondary metabolites that were purified and placed in our natural products library, which was 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 μM. 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 μM). 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. ablicans 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 μM), which makes this an intriguing model compound for studying the adjunctive use of biofilm inhibitors in combination with standard antifungal antibiotics.
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白色念珠菌在阴道粘膜上形成生物膜。
DOI：
10.1099/mic.0.039354-0
发表时间：
2010-12
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Harriott MM;Lilly EA;Rodriguez TE;Fidel PL;Noverr MC
通讯作者：
Noverr MC
影响因子：
15
作者：
Herzon, SB;Myers, AG
通讯作者：
Myers, AG
影响因子：
3
作者：
MURPHY, WS
通讯作者：
MURPHY, WS
影响因子：
14.8
作者：
Hoye, Thomas R.;Jeffrey, Christopher S.;Shao, Feng
通讯作者：
Shao, Feng
Notoamides A-D:: 从一种源自海洋的真菌 Aspergillus sp.
影响因子：
16.6
作者：
Kato, Hikaru;Yoshida, Takushi;Tsukamoto, Sachiko
通讯作者：
Tsukamoto, Sachiko