Mutation underlying resistance of Plasmodium berghei to atovaquone in the quinone binding domain 2 (QO2) of the cytochrome b gene
Mutation underlying resistance of Plasmodium berghei to atovaquone in the quinone binding domain 2 (QO2) of the cytochrome b gene
复制标题
DOI：
10.1016/j.parint.2007.12.002
复制
发表时间：
2008-06-01
影响因子：
1.9
通讯作者：
Marzuki, Sangkot
中科院分区：
文献类型：
--
作者：
Siregar, Josephine E.;Syafruddin, Din;Marzuki, Sangkot
抗疟药阿托伐醌特异性靶向细胞色素bc(1)复合体并抑制寄生虫呼吸。对这种辅酶Q类似物的耐药性与线粒体细胞色素b基因的突变有关。我们之前报道了伯氏疟原虫细胞色素b基因（M133I和L144S）的第一个醌结合域（Qo(1)）和第6个跨膜结构域的V284F的阿托伐醌耐药突变。然而，在恶性疟原虫中，最常见的突变发生在Qo(2)区。为了获得更好的生化和遗传研究模型，我们现在已经扩展了我们的研究，以分离更广泛的柏氏弧菌耐药菌株，特别是Qo中的菌株(2)。在这里，我们报道了四个新的突变（Y268N, Y268C， L271 V和K272R），它们都位于Qo(2)结构域。其中两个突变与药物诱导的疟原虫密码子268 （nt802-804）突变趋同。(2007爱思唯尔爱尔兰有限公司版权所有。
The anti-malarial agent atovaquone specifically targets the cytochrome bc(1) complex and inhibits the parasite respiration. Resistance to this drug, a coenzyme Q analogue, is associated with mutations in the mitochondrial cytochrome b gene. We previously reported atovaquone resistant mutations in Plasmodium berghei, in the first quinone binding domain (Qo(1)) of the cytochrome b gene (M133I and L144S) with V284F in the sixth transmembrane domain. However, in P. falciparum the most common mutations are found in the Qo(2) region. To obtain a better model for biochemical and genetic studies, we have now extended our study to isolate a wider range of R berghei resistant strains, in particular those in the Qo(2). Here we report four new mutations (Y268N, Y268C, L271 V and K272R), all in the Qo(2) domain. Two of these mutations are convergent to codon 268 (nt802-804) drug-induced mutation in P fialciparum. (0 2007 Elsevier Ireland Ltd. All rights reserved.