Effect of Cholesterol Content on Gramicidin S-Induced Hemolysis of Erythrocytes |
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Authors: | Ellen V Hackl Vladimir P Berest Sergey V Gatash |
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Institution: | (1) Department of Biomedical and Medical Physics, Karazin Kharkiv National University, Kharkiv, Ukraine;(2) Present address: Faculty of Health and Life Sciences, De Montfort University, Leicester, UK |
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Abstract: | Gramicidin S (GS) is a cyclo-decapeptide antibiotic with wide Gram+ and Gram− antimicrobial spectrum. However, its therapeutic
application is very limited due to hemolytic activity of GS. The presence of cholesterol defines one of the most significant
differences between eukaryotic plasma membranes and bacterial inner membranes. To find out the cholesterol effect on the GS
hemolytic efficiency we compared GS-induced hemolysis of erythrocytes extracted from the blood of healthy donors against donors
with atherosclerosis, “naturally” enriched with cholesterol. Our results show that increased cholesterol levels significantly
attenuates yet does not abolishes the GS hemolytic activity. High levels of cholesterol content in erythrocyte membranes results
in a decrease in the membrane fluidity and deformability leading to a decrease in the rate of GS interaction with membranes.
The results obtained confirm that hydrophobic as well as electrostatic interactions must be involved in the binding of GS
to cell membranes. Lipid peroxidation occurring within atherosclerotic erythrocytes leads to considerable decrease in the
degree of GS-induced erythrocyte hemolysis in vitro. These results can be applied to the rational design of GS analogs with
increased antibacterial efficiency but reduced hemolytic activity. |
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Keywords: | |
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