| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
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).
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