Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012, Berne, Switzerland.
Proteomics & Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Berne, Freiburgstrasse 15, CH-3010, Berne, Switzerland.
Int J Parasitol Drugs Drug Resist. 2019 Apr;9:112-119. doi: 10.1016/j.ijpddr.2019.03.002. Epub 2019 Mar 15.
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 O 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.
为了阐明阴道毛滴虫对硝基药物的耐药性是否归因于共同的耐药标记物,我们在存在两种硝基药物甲硝唑和硝唑尼特的情况下培养了三种耐药阴道毛滴虫株(C4、1062ID10 和 713M3)的滋养体,并通过对其蛋白质组的质谱shotgun 分析,将它们与其相应的野生型(WBC6、106 和 713)进行了比较。根据菌株和硝基药物的不同,鉴定出了超过 200 到 500 种差异表达的蛋白质,但在菌株和药物之间没有共同的模式。所有耐药株都经历了抗原变异,具有独特的表面抗原,如变异表面蛋白或富含半胱氨酸的蛋白,具体取决于菌株和硝基化合物。对涉及硝基还原和硝基自由基、NO 或 O 解毒的酶的进一步研究表明,每种药物和每种菌株都存在独特的策略。因此,我们得出结论,阴道毛滴虫对硝基药物的耐药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。