THE BACTERICIDAL ACTION OF STREPTOMYCIN - MEMBRANE PERMEABILIZATION CAUSED BY THE INSERTION OF MISTRANSLATED PROTEINS INTO THE CYTOPLASMIC MEMBRANE OF ESCHERICHIA-COLI AND SUBSEQUENT CAGING OF THE ANTIBIOTIC INSIDE THE CELLS DUE TO DEGRADATION OF THESE PROTEINS
THE BACTERICIDAL ACTION OF STREPTOMYCIN - MEMBRANE PERMEABILIZATION CAUSED BY THE INSERTION OF MISTRANSLATED PROTEINS INTO THE CYTOPLASMIC MEMBRANE OF ESCHERICHIA-COLI AND SUBSEQUENT CAGING OF THE ANTIBIOTIC INSIDE THE CELLS DUE TO DEGRADATION OF THESE PROTEINS
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DOI：
10.1099/00221287-138-3-551
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发表时间：
1992-03-01
期刊：
影响因子：
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通讯作者：
BAKKER, EP
中科院分区：
文献类型：
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作者：
BUSSE, HJ;WOSTMANN, C;BAKKER, EP
对氨基糖苷类抗生素链霉素透过大肠杆菌细胞质膜的机制进行了重新研究。为此，以低K+浓度下生长的细胞在链霉素诱导下K+损失的程度作为膜通透性的衡量标准。用不同的K+吸收突变体进行的实验表明，这种抗生素特异性地增加了细胞膜对K+和其他离子的被动通透性。这些通透性变化很小，处理细胞的膜电位仍然很高。膜的通透性不是由于抗生素与细胞膜的直接相互作用，因为携带rpsL突变并以链霉素不敏感的方式合成蛋白质的细胞在加入抗生素后不会失去K+。由于误读和翻译的提前终止，细胞在发生膜通透性的条件下合成了异常蛋白质。描述了两种情况，在这种情况下，细胞迅速降解这些错误翻译的蛋白质并重新积累K+，这支持了膜通透性是由于细胞膜中存在错误翻译的蛋白质的假说。有证据表明，不含抗生素的细胞对(二氢)链霉素摄取的不可逆性也可能是由于错误翻译的蛋白质迅速降解，导致抗生素在细胞内“笼子”。
The mechanism by which the aminoglycoside antibiotic streptomycin permeabilizes the cytoplasmic membrane of Escherichia coli cells was reinvestigated. For this purpose, the extent of streptomycin-induced K+ loss from cells growing at low external K+ concentrations was taken as a measure of membrane permeabilization. Experiments with different K+-uptake mutants showed that the antibiotic specifically increased the passive permeability of the cell membrane to K+ and other ions. These permeability changes were small and the membrane potential of the treated cells remained high. The membrane permeabilization was not due to a direct interaction of the antibiotic with the cell membrane, since cells that carry an rpsL mutation and synthesize proteins in a streptomycin-insensitive way did not lose K+ after the addition of the antibiotic. Due to misreading and premature termination of translation the cells synthesized aberrant proteins under the conditions where membrane permeabilization occurred. Two conditions are described under which the cells both degraded these mistranslated proteins rapidly and reaccumulated K+, lending support to the hypothesis that membrane permeabilization is due to the presence of the mistranslated proteins in the cell membrane. Evidence is presented that the irreversibility of (dihydro)streptomycin uptake by cells washed free from the antibiotic might also be due to rapid degradation of the mistranslated proteins, leading to 'caging' of the antibiotic inside the cells.