Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
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DOI：
10.1371/journal.pone.0007025
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发表时间：
2009-09-14
期刊：
影响因子：
3.7
通讯作者：
Mylonakis E
中科院分区：
文献类型：
--
作者：
Okoli I;Coleman JJ;Tampakakis E;An WF;Holson E;Wagner F;Conery AL;Larkins-Ford J;Wu G;Stern A;Ausubel FM;Mylonakis E
白色念珠菌是最常见的人类致病性真菌，它可以在微小的线虫秀丽隐杆线虫的肠道中建立持久的致命感染。解析：选c。白念珠菌感染模型以前适用于筛选抗真菌化合物。对该筛选进行了修改，以促进高通量测定，包括线虫与白色念珠菌的共接种和仪器，允许将蠕虫精确分配到测定井中，消除了两个劳动密集型步骤。利用这种高通量方法筛选了3228个化合物库，其中包括1948个生物活性化合物和1280个通过多样性导向合成获得的小分子。19种化合物被鉴定出可以提高秀丽隐杆线虫的存活率，包括化学文库中大多数已知的抗真菌化合物。除7种临床使用的抗真菌化合物外，还鉴定出12种非主要用作抗真菌药物的化合物，其中包括3种免疫抑制药物。该试验还允许在一次试验中评估化合物的相对最小抑制浓度、体内有效浓度和毒性。
Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
4.7
作者：
Artal-Sanz, Marto;de Jong, Liesbeth;Tavernarakis, Nektarios
通讯作者：
Tavernarakis, Nektarios
影响因子：
11.8
作者：
Edmond, MB;Wallace, SE;Wenzel, RP
通讯作者：
Wenzel, RP
影响因子：
6.7
作者：
Breger J;Fuchs BB;Aperis G;Moy TI;Ausubel FM;Mylonakis E
通讯作者：
Mylonakis E
影响因子：
3.1
作者：
Davis, D;Edwards, JE;Ibrahim, AS
通讯作者：
Ibrahim, AS