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Action mechanism of cationic drugs increasing the permeability of an outer membrane of Gram-negative bacteria

阳离子药物增加革兰氏阴性菌外膜通透性的作用机制

基本信息

批准号：
62570967
负责人：
KATSU Takashi
金额：
$ 1.28万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

A cationic antibiotic gramicidin S is known to increase the permeability of an outer membrane of Gram-megative bacteria. To clarify the mechanism of permeability increase, we tried to determine the size of lesion formed in membrane at first. For this porpose, we used erythrocytes, since the size of lesion could easily be determined by means of "osmotic protection experiment". It was observed that size of lesion increased with increasing the concentration of gramicidin S. Moreover, we observed the release of membrane fragments containing phospholipids under the conditions of membrane lesion. Gramicidin S caused a morphological change in human erythrocytes from normal discoid to crenated form. We supposed that gramicidin S molecules were predominantly accumulated in the outher half of lipid bilayer, deforming the erythrocyte cell into crenature. A large accumulation made the membrane structure unstable, resulting in the release of membrane fragments and the enhancement of permeability simultaneously. Next, we examined the action of gramicidin S on Staphylococcus aureus. Also, in this case, the release of phospholipids was stimulated in a concentration range causing permeability change. The antibiotic acted similarly on Escherichia coli cells, though the permeability change of E. COLI cells was not so dominant as those of S. aureus cells and erythrocytes. Here, it should be noted that E. COLI belonging to Gram-negative bacteria has outer membrane in the cell structure. Although gramicidin S induced markedly the release of lipopolysaccharide rich in the outer membrane, the size of lesion formed in the outer memgrane was significantly small. Thus, the antibiotic was difficult to intrude deeper into the cytoplasmic membrane, decreasing a permeability enhancement. We described here the results of gramicidin S only. Other results obtained through the present study have also been published (see references).

已知阳离子抗生素短杆菌肽S可增加革兰氏阴性菌外膜的渗透性。为了阐明渗透性增加的机制，我们首先尝试确定膜中形成的损伤的大小。为此，我们使用红细胞，因为通过“渗透保护实验”可以轻松确定病变的大小。观察到损伤的大小随着短杆菌肽S浓度的增加而增加。此外，我们观察到在膜损伤的条件下含有磷脂的膜碎片的释放。短杆菌肽 S 导致人红细胞形态发生变化，从正常的盘状变为圆齿状。我们推测短杆菌肽S分子主要积聚在脂质双层的外半部分，使红细胞变形为生物体。大量积累使膜结构不稳定，导致膜碎片释放，同时导致渗透性增强。接下来，我们检查了短杆菌肽 S 对金黄色葡萄球菌的作用。另外，在这种情况下，在引起渗透性变化的浓度范围内刺激磷脂的释放。抗生素对大肠杆菌细胞的作用类似，但大肠杆菌细胞的通透性变化并不像金黄色葡萄球菌细胞和红细胞那样显着。这里，应该注意的是，属于革兰氏阴性菌的大肠杆菌在细胞结构中具有外膜。尽管短杆菌肽S显着诱导外膜富含脂多糖的释放，但外膜中形成的损伤尺寸明显较小。因此，抗生素难以更深入地侵入细胞质膜，从而降低了通透性的增强。我们在此仅描述了短杆菌肽 S 的结果。通过本研究获得的其他结果也已发表（参见参考文献）。