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杜氏利什曼原虫对sitamaquine耐药前鞭毛体的筛选及表型特征分析

Selection and phenotype characterisation of sitamaquine-resistant promastigotes of Leishmania donovani.

作者信息

Bories Christian, Cojean Sandrine, Huteau Françoise, Loiseau Philippe M

机构信息

Groupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Univ Paris-Sud 11, 92290-Châtenay-Malabry, France.

出版信息

Biomed Pharmacother. 2008 Mar;62(3):164-7. doi: 10.1016/j.biopha.2007.12.006. Epub 2008 Jan 14.

Abstract

A Leishmania donovani promastigote line resistant to 160microM sitamaquine, named SITA-160R, was selected in vitro by continuous stepwise drug pressure. SITA-160R line was able to infect murine peritoneal macrophages in vitro in the same manner as the wild-type line (WT) but was less infective for Balb/c mice than its parent WT clone. This line was about five and three times more resistant to sitamaquine than the WT line on promastigote and intramacrophage amastigote forms, respectively. No cross-resistance with other antileishmanial agents was observed and this resistance was stable when parasites were subcultured in drug-free medium for a long time or after in vivo passage.

摘要

通过连续逐步施加药物压力,在体外筛选出了对160微摩尔西他喹啉具有抗性的杜氏利什曼原虫前鞭毛体株系,命名为SITA-160R。SITA-160R株系能够以与野生型株系(WT)相同的方式在体外感染小鼠腹腔巨噬细胞,但对Balb/c小鼠的感染性低于其亲本WT克隆。该株系对前鞭毛体和巨噬细胞内无鞭毛体形式的西他喹啉的抗性分别比WT株系高约5倍和3倍。未观察到与其他抗利什曼原虫药物的交叉抗性,并且当寄生虫在无药物培养基中长期传代培养或体内传代后,这种抗性是稳定的。

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