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首页> 外文期刊>Parasitology >High-throughput screening in suboptimal growth conditions identifies agonists of Giardia lamblia proliferation.
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High-throughput screening in suboptimal growth conditions identifies agonists of Giardia lamblia proliferation.

机译:在不理想的生长条件下进行高通量筛选可鉴定出贾第鞭毛虫增殖的激动剂。

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摘要

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.
机译:贾第鞭毛虫是人类最普遍的寄生虫之一,估计每年引起超过2亿例感染。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,并鉴定了多种抑制剂。在这里,我们使用改良的分析方法来筛选促进滋养体繁殖的化合物。通过稀释培养基减少滋养体的生长,并延长生长期以筛选2个包含1500种化合物的化合物文库。总共鉴定了4种滋养体增殖的激动剂。在这些化合物中的一种存在的情况下,士的宁增强了生长,并伴随着不寻常的滋养体形态,其特征是滋养体分裂成每个细胞显示出超过2个核,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,但已知会影响异戊二烯化,表明蛋白质或脂质异戊二烯化与培养物之间存在联系。尽管已知异戊二烯化的抑制剂可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尚未在前面描述。这些观察结果说明了化学遗传学在识别控制兰氏菌特定性状的途径中的作用。

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