High-throughput screening in suboptimal growth conditions identifies agonists of Giardia lamblia proliferation.
High-throughput screening in suboptimal growth conditions identifies agonists of Giardia lamblia proliferation.
复制标题
在次优生长条件下进行高通量筛选，鉴定兰氏贾第鞭毛虫增殖的激动剂。
DOI：
10.1017/s0031182010001101
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发表时间：
2011
期刊：
影响因子：
2.4
通讯作者：
Widmer,G
中科院分区：
文献类型：
--
作者：
Faghiri,Z;Santiago,RBonilla;Wu,Z;Widmer,G
蓝氏贾第虫是人类最普遍的寄生虫之一，估计每年造成超过2亿人感染。为了筛选干扰滋养体增殖的化合物的化学文库，我们将常规培养方法应用于384孔板，并鉴定了许多抑制剂。在这里，我们使用了一种改良的检测方法来筛选促进滋养体增殖的化合物。通过稀释培养基减少滋养体生长，并延长生长期以筛选包含1500种化合物的2个化合物文库。共鉴定了4种滋养体增殖激动剂。在这些化合物之一，士的宁的存在下，增强的生长伴随着不寻常的滋养体形态，其特征在于分裂的滋养体显示超过2个细胞核，这是通常观察到的。其他激动剂，虽然属于2个不同的化学基团，已知影响异戊二烯化，表明蛋白质或脂质异戊二烯化和培养物中的生长之间的联系。尽管已知异戊二烯化的抑制剂拮抗哺乳动物细胞的增殖，但据我们所知，异戊二烯化调节剂的激动作用以前没有描述过。这些观察结果说明了化学遗传学在确定控制G.兰布利亚
Giardia lamblia is one of the most prevalent parasites of mankind and is estimated to cause over 200 million infections per year. To screen chemical libraries for compounds that perturb trophozoite proliferation we adapted a conventional culture method to 384-well plates and identified numerous inhibitors. Here we used a modified assay to screen for compounds that promote trophozoite multiplication. Trophozoite growth was reduced by dilution of the culture medium and the growth period was extended to screen 2 compound libraries comprising 1500 compounds. A total of 4 agonists of trophozoite multiplication were identified. In the presence of one of these compounds, strychnine, enhanced growth was accompanied by unusual trophozoite morphology characterized by dividing trophozoites displaying more than the 2 nuclei per cell which are normally observed. The other agonists, although belonging to 2 distinct chemical groups, are known to affect isoprenylation, indicating a link between protein or lipid isoprenylation and growth in culture. Although inhibitors of isoprenylation are known to antagonize proliferation of mammalian cells, an agonistic effect of isoprenylation modulators has to our knowledge not been described previously. These observations illustrate the power of chemical genetics for identifying pathways controlling specific traits in G. lamblia.