Genetic analysis of resistance to benzimidazoles in Physarum: differential expression of beta-tubulin genes.
Genetic analysis of resistance to benzimidazoles in Physarum: differential expression of beta-tubulin genes.
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绒泡菌对苯并咪唑耐药性的遗传分析：β-微管蛋白基因的差异表达。
DOI：
10.1093/genetics/108.1.123
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发表时间：
1984
期刊：
影响因子：
3.3
通讯作者：
Dove,WF
中科院分区：
文献类型：
--
作者：
Burland,TG;Schedl,T;Gull,K;Dove,WF
绒泡菌显示两种营养细胞类型，单核黏性阿米巴原虫和多核疟原虫。对抗微管蛋白药物甲基苯并咪唑-2-酰基氨基甲酸酯（MBC）耐药的绒泡菌粘阿米巴突变体进行了分离。所有测试的突变体对其他苯并咪唑具有交叉抗性，但对环己亚胺或艾美汀没有交叉抗性。遗传分析表明，对MBC抗性的突变可以发生在4个非连锁位点benA、benB、bencobend中的任何一个位点。benbandbendmutants的MBC抗性在疟原虫中表达，但bena1和bencendmutants的疟原虫对MBC敏感，表明bena2和bencendmutants编码黏黏性阿米巴特异性产物。携带隐性bend210突变的粘阿米巴虫除了表达具有野生型迁移率的β-微管蛋白外，还表达具有新电泳迁移率的β-微管蛋白。这和其他证据表明，bendi是β-微管蛋白的结构基因，并且至少有两个β-微管蛋白基因在粘变形虫中表达。通过凝胶电泳比较野生型和bend210菌株的β-微管蛋白，发现绒泡菌中表达的3个（或更多）β-微管蛋白基因中，有一个基因benD在黏性阿米巴原虫和疟原虫中均有表达，一个在黏性阿米巴原虫中特异性表达，一个在疟原虫中特异性表达。然而，仅一个基因的突变，benD，就足以使粘阿米巴原虫和疟原虫对MBC产生耐药性。
Physarum displays two vegetative cell types, uninucleate myxamoebae and multinucleate plasmodia. Mutant myxamoebae of Physarum resistant to the antitubulin drug methylbenzimidazole-2-yl-carbamate (MBC) were isolated. All mutants tested were cross-resistant to other benzimidazoles but not to cycloheximide or emetine. Genetic analysis showed that mutation to MBC resistance can occur at any one of four unlinked loci,benA, benB, benCorbenD. MBC resistance ofbenBandbenDmutants was expressed in plasmodia, butbenAandbenCmutant plasmodia were MBC sensitive, suggesting thatbenAandbenCencode myxamoeba-specific products. Myxamoebae carrying the recessivebenD210mutation express a β-tubulin with noval electrophoretic mobility, in addition to a β-tubulin with wild-type mobility. This and other evidence indicates thatbenDis a structural gene for β-tubulin, and that at least two β-tubulin genes are expressed in myxamoebae. Comparisons of the β-tubulins of wildtype andbenD210strains by gel electrophoresis revealed that, of the three (or more) β-tubulin genes expressed inPhysarum, one,benD, is expressed in both myxamoebae and plasmodia, one is expressed specifically in myxamoebae and one is expressed specifically in plasmodia. However, mutation in only one gene,benD, is sufficient to confer MBC resistance on both myxamoebae and plasmodia.