Cycloheximide efflux in antibiotic-adapted cells of the fungus Mucor racemosus.
Cycloheximide efflux in antibiotic-adapted cells of the fungus Mucor racemosus.
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真菌毛霉的抗生素适应细胞中放线菌酮的流出。
DOI：
10.1128/aac.32.3.341
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发表时间：
1988
影响因子：
4.9
通讯作者：
Sypherd,PS
中科院分区：
文献类型：
--
作者：
ShearerJr,G;Sypherd,PS
适应环己亚胺或木霉胺的总状毛霉细胞对环己亚胺的抗性比未适应的细胞高约40倍。在体外多聚(U)翻译实验中，从适应细胞和非适应细胞分离的核糖体对环己亚胺同样敏感。适应细胞没有检测到环己亚胺的修饰。非适应细胞和适应细胞摄取药物的特点是，在[3H]环己亚胺孵育的前2分钟内，药物迅速积累，随后细胞内药物浓度稳定在远低于培养基的水平。适应细胞的稳态药物浓度大约比未适应细胞低10倍。叠氮化钠或二硝基酚处理细胞消除了非适应细胞和适应细胞对药物摄取的差异，使细胞内药物水平与培养基相等。直接外排测量表明，负载环己亚胺的适应细胞能够比未适应的细胞更快地排泄药物。这些结果表明，非适应细胞和适应细胞都具有能量依赖的转运环己亚胺外排机制，适应细胞的抗性是由于转运效率的提高。
Mucor racemosus cells adapted to either cycloheximide or trichodermin were approximately 40-fold more resistant to cycloheximide than nonadapted cells. Ribosomes isolated from adapted and nonadapted cells were equally sensitive to cycloheximide in an in vitro poly(U) translation assay. There was no detectable modification of cycloheximide by adapted cells. Uptake of drug by nonadapted and adapted cells was characterized by a rapid initial accumulation during the first 2 min of incubation with [3H]cycloheximide, followed by a steady-state intracellular drug concentration well below that of the medium. The steady-state drug concentration was approximately 10-fold lower in adapted cells than in nonadapted cells. Treatment of cells with sodium azide or dinitrophenol abolished the difference between uptake of drug by nonadapted and adapted cells and resulted in intracellular drug levels equal to that of the medium. Direct efflux measurements showed that adapted cells loaded with cycloheximide were able to excrete the drug far more rapidly than nonadapted cells. These results suggest that both nonadapted and adapted cells possess an energy-dependent efflux mechanism for transporting cycloheximide and that resistance in adapted cells is due to increased efficiency of transport.