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Resistance formation to nitro drugs in Giardia lamblia: No common markers identified by comparative proteomics.
International Journal for Parasitology: Drugs and Drug Resistance ( IF 4.1 ) Pub Date : 2019-03-20 , DOI: 10.1016/j.ijpddr.2019.03.002
Joachim Müller 1 , Sophie Braga 2 , Manfred Heller 2 , Norbert Müller 1
Affiliation  

In order to elucidate the question whether resistance to nitro drugs in G. lamblia is due to common resistance markers, trophozoites of three resistant G. lamblia strains, namely C4, 1062ID10, and 713M3 were grown in the presence of the two nitro drugs metronidazole and nitazoxanide and compared to their corresponding wild-types WBC6, 106, and 713 by mass spectometry shotgun analysis of their proteomes. Depending on the strain and the nitro drug, more than 200 to 500 differentially expressed proteins were identified, but there were no common patterns across strains and drugs. All resistant strains underwent antigenic variation with distinct surface antigens like variant surface proteins or cysteine rich proteins depending on strain and nitro compound. A closer look on enzymes involved in nitroreduction and detoxification of nitro radicals, NO or O2 suggested the existence of distinct strategies for each drug and each strain. Therefore, we conclude that resistance to nitro drugs in G. lamblia is not correlated with a specific pattern of differentially expressed proteins and therefore seems not to be the result of a directed process.

中文翻译:

贾第鞭毛虫对硝基药物的耐药性形成:比较蛋白质组学未鉴定出常见标记。

为了阐明是否存在对兰氏革兰氏菌对硝基药物产生抗药性的问题是由于常见的抗药性标记,在两种硝基药物甲硝唑和甲硝唑存在的情况下,生长了三种抗性兰氏菌菌株(C4、1062ID10和713M3)的滋养体。并用其蛋白质组的质谱shot弹枪分析将其与相应的野生型WBC6、106和713进行比较。根据菌株和硝基药物的不同,可以鉴定出200至500多种差异表达的蛋白质,但是在菌株和药物之间没有共同的模式。根据菌株和硝基化合物,所有抗性菌株都经过具有独特表面抗原(如变异表面蛋白或富含半胱氨酸的蛋白)的抗原变异。仔细研究与硝基自由基的硝基还原和解毒有关的酶,NO或O2提示每种药物和菌株均存在不同的策略。因此,我们得出结论,对兰伯氏菌中硝基药物的抗性与差异表达蛋白的特定模式无关,因此似乎不是定向过程的结果。
更新日期:2019-11-01
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