Mechanisms of Selective Antimicrobial Activity of Gaegurin 4

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Kim, Heejeong; Lee, Byeong Jae; Lee, Mun Han; Hong, Seong Geun; Ryu, Pan Dong
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대한약리학회 = The Korean Journal of Physiology & Pharmacology
Korean J Physiol Pharmacol 13: 39-47, 2009
Antimicrobial peptideCell selectivityLipid compositionPlanar lipid bilayerK+ efflux
Gaegurin 4 (GGN4), an antimicrobial peptide isolated from a Korean frog, is five times more potent
against Gram-positive than Gram-negative bacteria, but has little hemolytic activity. To understand
the mechanism of such cell selectivity, we examined GGN4-induced K+ efflux from target cells, and
membrane conductances in planar lipid bilayers. The K+ efflux from Gram-positive M. luteus (2.5 μg/ml)
was faster and larger than that from Gram-negative E. coli (75 μg/ml), while that from RBC was
negligible even at higher concentration (100 μg/ml). GGN4 induced larger conductances in the planar
bilayers which were formed with lipids extracted from Gram-positive B. subtilis than in those from
E. coli (p<0.01), however, the effects of GGN4 were not selective in the bilayers formed with lipids
from E. coli and red blood cells. Addition of an acidic phospholipid, phosphatidylserine to planar
bilayers increased the GGN4-induced membrane conductance (p<0.05), but addition of
phosphatidylcholine or cholesterol reduced it (p<0.05). Transmission electron microscopy revealed that
GGN4 induced pore-like damages in M. luteus and dis-layering damages on the outer wall of E. coli.
Taken together, the present results indicate that the selectivity of GGN4 toward Gram-positive over
Gram-negative bacteria is due to negative surface charges, and interaction of GGN4 with outer walls.
The selectivity toward bacteria over RBC is due to the presence of phosphatidylcholine and cholesterol,
and the trans-bilayer lipid asymmetry in RBC. The results suggest that design of selective
antimicrobial peptides should be based on the composition and topology of membrane lipids in the
target cells.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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